A Phase I Study to Evaluate the Taste of Belumosudil Oral Suspensions & Assess Relative Bioavailability

• Status: Completed
• Trial end date: 2021-07-08
• Target enrollment: 0
• Participant gender: Male

Summary

This is a single-center, randomized, open-label, 2-part study in healthy male subjects to evaluate the taste profile of different belumosudil oral suspensions and the relative bioavailability of those chosen oral suspensions of belumosudil compared to oral tablets of belumosudil.

Part 1 is an open-label, randomized single-period study of oral suspensions of belumosudil 40 mg/mL delivered in 6 different vehicles. Approximately 12 healthy male subjects, 2 subjects in each of 6 groups, will be administered a single dose of belumosudil 40 mg/mL in 6 different vehicles (Vehicles 1, 2, 3, 4, 5, and 6) in corresponding Regimens A, B, C, D, E, and F in different sequences of the 6 vehicles. All subjects will receive 1 dose of all belumosudil in all 6 vehicles which are as follows: ABFCED; BCADFE; CDBEAF; DECFBA; EFDACB; and FAEBDC.

Part 2 is a single-center, open-label, randomized, 3-period design to assess the relative bioavailability of a selected belumosudil suspension formulation compared to the oral belumosudil. Tablet reference and the effect of food on the selected belumosudil suspension formulation in 18 healthy male subjects. Subjects will be randomized prior to the administration of the first dose of IMP to 1 of 6 treatment sequences (GHI, HIG, IGH, IHG, GIH and HGI), with 3 subjects assigned to each treatment sequence where:

Regimen G--oral belumosudil 200 mg tablet (reference) with the subject fed; Regimen H--belumosudil powder 200 mg for oral suspension or belumosudil 200 mg oral suspension with the subject fasting; and Regimen I--belumosudil 200 mg powder for oral suspension or belumosudil 200 mg oral suspension with the subject fed.

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

Details

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

Criteria

Inclusion Criteria:

1. Healthy males

2. Aged 18 to 55 years inclusive at the time of signing informed consent.

3. Body mass index of 18.0 to 32.0 kg/m^2 at screening

4. Body weight ≥ 50 kg at screening

5. Must be willing and able to communicate and participate in the entire study

6. Must provide written informed consent

7. Must agree to adhere to the contraception requirements

Exclusion Criteria:

1. Subjects who have received any IMP in a previous clinical research study within the 90 days prior to Day 1 (Part 2 only)

2. Subjects who are or are immediate family members of a study site or sponsor employee

3. Subjects who have previously been administered IMP in Part 2 of this study. Subjects who have taken part in Part 1 are permitted to take part in Part 2

4. Evidence of current SARS-CoV-2 infection

5. Clinically significant history or presence of acute or chronic bacterial, fungal, or viral infection (e.g., pneumonia, septicemia) within the 3 months or 90 days prior to screening

6. Any subject with clinically significant symptoms of COVID-19 in the last 4 weeks, including but not limited to fever, new and persistent cough, breathlessness or loss of taste or smell, as per the judgement of the investigator

7. Known or suspected malignancy, autoimmune disorder, or any history of known or suspected congenital or acquired immunodeficiency state or condition that would compromise the participant's immune status or any factor that would predispose participants to develop infection (e.g., open skin lesions, recurrent issues related to poor dentition, perianal fissures, history of splenectomy, primary immunodeficiency)

8. History of any drug or alcohol abuse in the past 2 years

9. Regular alcohol consumption in males > 21 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirits, 1.5 to 2 units = 125 mL glass of wine, depending on type)

10. A confirmed positive alcohol breath test at screening or admission

11. Current smokers and those who have smoked within the last 12 months. A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or admission.

12. Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months

13. Subjects with pregnant or lactating partners

14. Subjects who do not have suitable veins for multiple venipunctures/cannulation as assessed by the investigator or delegate at screening

15. Clinically significant abnormal clinical chemistry, hematology or urinalysis as judged by the investigator. Subjects with Gilbert's Syndrome are allowed.

16. Confirmed positive drugs of abuse test result.

17. Positive hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus antibody results

18. Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance (CLcr) of < 80 mL/min using the Cockcroft-Gault equation (Part 2 only)

19. History of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory, gastrointestinal (GI) disease, or neurological or psychiatric disorder as judged by the investigator

20. Subject has a history or presence of any of the following (Part 2 only):

• Cytopenias

• Active GI disease requiring therapy

• Hepatic disease and/or alanine aminotransferase or aspartate aminotransferase > upper limit of normal (ULN)

• Renal disease and/or serum creatinine > ULN

• Other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs

21. Subjects with a history of cholecystectomy or gall stones (Part 2 only)

22. Subject has QTcF intervals >450 msec at screening or admission (Part 2 only)

23. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients

24. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active

25. Donation of blood or plasma within the previous 3 months or loss > 400 mL of blood

26. Subjects who are taking or have taken any prescribed or over-the-counter drug or herbal remedies (other than up to 4 g of paracetamol per day) in the 14 days prior to IMP administration, including proton pump inhibitors. Exceptions may apply on a case by case basis, if considered not to interfere with the objectives of the study, as determined by the investigator.

27. Failure to satisfy the investigator of fitness to participate for any other reason