Human Absorption, Distribution and Metabolism Study (hAME) [14C]-KD025
Condition: Autoimmune Diseases; Fibrosis
MeSH terms: Autoimmune Diseases
Intervention: Belumosudil 200 mg tablet; [14C]-KD025 at a dose of 100 μg in a 5 mL solution IV microdose; [14C]-KD025 200 mg capsule
Intervention description: Belumosudil 200 mg tablet, development candidate; test investigational medicinal product; test investigational medicinal product
Intervention MeSH terms: Belumosudil
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: Single center, non-randomized, open-label, 2-part study
Masking: None (Open Label)
Enrollment: 5.0
Sex: Male
Minimum age: 30 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: absorption; metabolism; excretion

Summary:

      Human, absorption, metabolism and excretion study of belumosudil (KD025)
    

Eligibility criteria:

        Inclusion Criteria:

          1. Healthy males

          2. Good state of health (mentally and physically) as indicated by a comprehensive
             clinical assessment (detailed medical history and a complete physical examination),
             electrocardiogram (ECG) and laboratory investigations (hematology, clinical chemistry
             and urinalysis)

          3. Body weight ≥ 50 kg

          4. Body mass index (BMI) of 18.0 to 35.0 kg/m^2

          5. Must be willing and able to communicate and participate in the whole study

          6. Must have regular bowel movements (i.e., average stool production of ≥ 1 and ≤ 3
             stools per day)

          7. Subjects must have participated in Part 1 in order to be eligible for Part 2

          8. Must provide written informed consent

          9. Must agree to adhere to the contraception requirements of the study

        In addition to the above criteria, subjects must agree to the following restrictions:

          -  No alcohol during the 24 hours prior to screening and the 24-hour prior to each
             admission until discharge from each part of the study.

          -  No food or drinks containing grapefruit, cranberry, caffeine or other xanthines from
             24 hours prior to each admission until discharge from each part of the study.

          -  No food containing poppy seeds for 48 hours prior to screening and for 48 hours prior
             to each admission until discharge from each part of the study.

          -  No unaccustomed strenuous exercise from the 72-hour period before the screening visit
             and then from 72 hours prior to each admission until discharge from each part of the
             study.

        Exclusion Criteria:

          1. Subjects who previously participated in any other investigational study drug trial in
             which receipt of an investigational study drug occurred within 90 days prior to dosing

          2. Subjects who have previously participated in a study where subjects were dosed with
             belumosudil

          3. Subjects who are study site employees or immediate family members of a study site or
             sponsor employee

          4. Subjects with pregnant partners

          5. History of any drug or alcohol abuse in the past 2 years

          6. Regular alcohol consumption in males > 21 units per week (1 unit = ½ pint beer, or a
             25 mL shot of 40% spirit, 1.5 to 2 Units = 125 mL glass of wine, depending on type)

          7. Current smokers and those who have smoked within the last 12 months. A breath carbon
             monoxide reading of greater than 10 ppm at screening and admission

          8. Current users of e-cigarettes and nicotine replacement products and those who have
             used these products within the last 12 months

          9. Radiation exposure, including that from the present study, excluding background
             radiation but including diagnostic x-rays and other medical exposures, exceeding 5 mSv
             in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker,
             as defined in the Ionizing Radiation Regulations 2017.

         10. Subjects who have been enrolled in an ADME/IV microtracer study in the last 12 months

         11. Subjects who do not have suitable veins for multiple venepunctures/cannulation

         12. Clinically significant abnormal biochemistry, hematology or urinalysis. Subjects with
             blood platelet count, hemoglobin and red blood cells lower than the reference range

         13. Confirmed positive drugs of abuse test result

         14. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab), or
             human immunodeficiency virus (HIV) results

         15. Evidence of renal impairment at screening as indicated by an estimated creatinine
             clearance of < 80 mL/min using the Cockcroft-Gault equation

         16. History of clinically significant cardiovascular, renal, hepatic, chronic respiratory
             or gastrointestinal (GI) disease, neurological or psychiatric disorder, as judged by
             the Investigator

         17. Subject has a history or presence of any of the following:

               -  Active GI disease requiring therapy

               -  Hepatic disease and/or alanine aminotransaminase or aspartate aminotransaminase >
                  upper limit of normal (ULN)

               -  Renal disease and/or serum creatinine > upper limit of normal (ULN)

               -  Other condition known to interfere with the absorption, distribution, metabolism
                  or excretion of drugs

         18. Subject has QT interval corrected using Fridericia's formula (QTcF) intervals > 450
             msec at screening or admission

         19. Serious adverse reaction or serious hypersensitivity to any drug or the formulation
             excipients

         20. Presence or history of clinically significant allergy requiring treatment

         21. Donation or loss of greater than 400 mL of blood within the previous 3 months

         22. Subjects who are taking, or have taken, any prescribed or over-the-counter drug or
             herbal remedies in the 14 days before study drug administration.

         23. Failure to satisfy the Investigator of fitness to participate for any other reason