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

NCT03907540 | Completed Phase 1 Results

• 2 other identifiers: KD025-1082018-004773-28
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Autoimmune Diseases; Fibrosis

Keywords

absorption; metabolism; excretion

Outcome Measures

Primary Outcomes (1)

• Part 1 Pharmacokinetics: t(1/2) for Belumosudil Tablet and [14C]-KD025 IV

  Apparent terminal elimination half-life (t\[1/2\] for Part 1: (Treatment A) KD025 200 mg tablet, fed (Day 1). then 1.75 hours later (Treatment B) \[14C\]-KD025 solution for infusion 20 microgm/mL (100 microgm in 5 mL) containing \<= 37 kilobecquerel as 15 min IV infusion 100 microgm, fed

  Plasma samples belumosudil relative to oral dosing: 0,0.5,1,1.5,2,3,4,5,6,8,10,12,24,36, and 48 hours post-dosing. Plasma samples [14C]-KD025 relative to end infusion:-0.25,-0.16,-0.08,0,0.08,0.16,0.25,0.5,0.75,1,1.5,2,3,4,5,6,8,10,12,22,34, and 46 h

Secondary Outcomes (11)

• Part 1 Pharmacokinetics: Tmax for Belumosudil Tablet and [14C]-KD025

  Plasma samples belumosudil relative oral dosing: 0,0.5,1,1.5,2,3,4,5,6,7,8,10,12,24,36, and 48 hours post-dosing. Plasma samples [14C]-KD025 relative to end infusion:-0.25,-0.16,-0.08,0,0.08,0.16,0.25,0.5,0.75,1, 1.5,2,3,4,5,6,8,10,12,22,34,and 46 h

• Part 1 Pharmacokinetics: Cmax of Belumosudil Tablets

  Plasma samples belumosudil relative to oral dosing: 0,0.5,1,1.5,2,3,4,5,6,7,8,10,12,24,36, and 48 hours post-dosing.

• Part 1 Pharmacokinetics: Cmax of [14C]-KD025 IV

  Plasma samples for [14C]-KD025 relative to end of infusion:-0.25,-0.16,-0.08,0,0.08,0.16,0.25,0.5,0.75,1, 1.5,2,3,4,5,6,8,10,12,22,34,46 hours post-dose

• Part 1 Pharmacokinetics: AUC(0-inf) of Belumosudil Tablets

  Plasma samples for belumosudil relative to oral dosing: 0,0.5,1,1.5,2,3,4,5,6,7,8,10,12,24,36, and 48 hours post-dosing.

• Part 1 Pharmacokinetics: AUC(0-inf) of [14C]-KD025 IV

  Plasma samples for [14C]-KD025 relative to end of infusion:-0.25,-0.16,-0.08,0,0.08,0.16,0.25,0.5,0.75,1, 1.5,2,3,4,5,6,8,10,12,22,34,and 46 hours post-dose

Study Arms (3)

Part 1, Treatment A--Belumosudil 200 mg Tablet

EXPERIMENTAL

Belumosudil 200 mg tablet

Drug: Belumosudil 200 mg tablet

Part 1, Treatment B--[14C]-KD025 IV Microdose

EXPERIMENTAL

\[14C\]-KD025 at a dose of 100 μg in a 5 mL solution containing NMT 37 kBq (1000 nCi) \[14C\] over 15 min IV

Drug: [14C]-KD025 at a dose of 100 μg in a 5 mL solution IV microdose

Part 2, Treatment C--[14C]-KD025 Capsule

EXPERIMENTAL

\[14C\]-KD025 200 mg capsule containing NMT 9.8 MBq (215 μCi)

Drug: [14C]-KD025 200 mg capsule

Interventions

Belumosudil 200 mg tablet DRUG

Belumosudil 200 mg tablet, development candidate

Also known as: Rezurock (brand name), KD025, SLx-2119

Part 1, Treatment A--Belumosudil 200 mg Tablet

[14C]-KD025 at a dose of 100 μg in a 5 mL solution IV microdose DRUG

test investigational medicinal product

Part 1, Treatment B--[14C]-KD025 IV Microdose

[14C]-KD025 200 mg capsule DRUG

test investigational medicinal product

Part 2, Treatment C--[14C]-KD025 Capsule

Eligibility Criteria

• Age: 30 Years - 65 Years
• Gender Eligibility Details: Healthy males
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy males
• 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)
• Body weight ≥ 50 kg
• Body mass index (BMI) of 18.0 to 35.0 kg/m\^2
• Must be willing and able to communicate and participate in the whole study
• Must have regular bowel movements (i.e., average stool production of ≥ 1 and ≤ 3 stools per day)
• Subjects must have participated in Part 1 in order to be eligible for Part 2
• Must provide written informed consent
• 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.

You may not qualify if:

• 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
• Subjects who have previously participated in a study where subjects were dosed with belumosudil
• Subjects who are study site employees or immediate family members of a study site or sponsor employee
• Subjects with pregnant partners
• History of any drug or alcohol abuse in the past 2 years
• 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)
• 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
• Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months
• 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.
• Subjects who have been enrolled in an ADME/IV microtracer study in the last 12 months
• Subjects who do not have suitable veins for multiple venepunctures/cannulation
• Clinically significant abnormal biochemistry, hematology or urinalysis. Subjects with blood platelet count, hemoglobin and red blood cells lower than the reference range
• Confirmed positive drugs of abuse test result
• Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab), or human immunodeficiency virus (HIV) results
• Evidence of renal impairment at screening as indicated by an estimated creatinine clearance of \< 80 mL/min using the Cockcroft-Gault equation

Sponsors & Collaborators

• Kadmon Corporation, LLC: lead
• Quotient Sciences: collaborator

Study Sites (1)

Quotient Sciences Ltd

Ruddington, Nottingham, NG11 6JS, United Kingdom

Location

Related Publications (1)

• Schueller O, Skucas E, Regev G, Shaw I, Singh N, Sanghvi M, Croft M, Lohmer L, Alabanza A, Patel J. Absolute Bioavailability, Mass Balance, and Metabolic Profiling Assessment of [14 C]-Belumosudil in Healthy Men: A Phase 1, Open-Label, 2-Part Study. Clin Pharmacol Drug Dev. 2022 Jul;11(7):786-794. doi: 10.1002/cpdd.1085. Epub 2022 Mar 1.

  PMID: 35231159 BACKGROUND

MeSH Terms

Conditions

Autoimmune Diseases; Fibrosis

Interventions

belumosudil; Tablets; KD025

Condition Hierarchy (Ancestors)

Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Olivier Schueller, Senior Vice President, CMC & Clinical Pharmacology
• Organization: Kadmon Corporation

olivier.schueller@kadmon.com

724-778-6170

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single center, non-randomized, open-label, 2-part study

Study Record Dates

• First Submitted: April 5, 2019
• First Posted: April 9, 2019
• Study Start: April 5, 2019
• Primary Completion: May 20, 2019
• Study Completion: May 20, 2019
• Last Updated: May 26, 2022
• Results First Posted: September 13, 2021

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)