Human Absorption, Distribution and Metabolism Study (hAME) [14C]-KD025

• Status: Completed
• Trial end date: 2019-05-20
• Target enrollment: 0
• Participant gender: Male

Summary

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

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Kadmon Corporation, LLC
• Collaborator: Quotient Sciences

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