Bioavailability of Belumosudil (KD025) in Healthy Male Subjects

NCT02557139 | Completed Phase 1 Results

• 2 other identifiers: KD025-1062015-002832-42
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Bioavailability

Outcome Measures

Primary Outcomes (2)

• Pharmacokinetics: Cmax of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose

  Maximum concentration (Cmax) of parent drug (KD025), Metabolite 1 (KD025m1), and Metabolite 2 (KD025m2) when administering a single dose of belumosudil 200 mg tablet to subjects who are fasting (Regimen A) compared to administering a single dose of belumosudil 200 mg tablet to subjects who are fed (Regimen B) at 48 hours after dosing

  Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose

• Pharmacokinetics: AUCs of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose

  Area under concentration-time curve from zero to last dose of belumosudil 200 mg tablets (AUC\[0-last\]) and from zero to infinity (AUC\[0-inf\]) for Metabolite 1 (KD025m1), and Metabolite 2 (KD025m2) when administering a single dose of belumosudil 200 mg tablet to subjects who are fasting (Regimen A) compared to administering a single dose of belumosudil 200 mg tablet to subjects who are fed (Regimen B) at 48 hours after dosing

  Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose

Secondary Outcomes (8)

• Pharmacokinetics: Cmax for the Relative Bioavailability of Regimen B/Regimen A and Regimen B/Regimen C by Ratio of the Adjusted Geometric Means at 48 Hours Post-dose

  Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose

• Pharmacokinetics: AUCs for the Relative Bioavailability of Regimen B/Regimen A and Regimen B/Regimen C by Ratio of the Adjusted Geometric Means at 48 Hours Post-dose

  Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose

• Pharmacokinetics: Cmax of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) vs. Dosing Regimen C (Capsules--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose

  Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose

• Pharmacokinetics: AUCs of Regimen A (Tablet--Fasting) vs. Dosing Regimen B (Tablet--Fed) vs. Dosing Regimen C (Capsule--Fed) for KD025, KD025m1, and KD025m2 for Belumosudil 200 mg at 48 Hours Post-dose

  Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose

• Pharmacokinetics: Lambda-z for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose

  Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose

Study Arms (3)

Regimen A

EXPERIMENTAL

Single-dose belumosudil 200 mg tablet in the fasted state

Drug: Belumosudil Tablet

Regimen B

EXPERIMENTAL

Single-dose belumosudil 200 mg tablet in the fed state

Drug: Belumosudil Tablet

Regimen C

EXPERIMENTAL

Single-dose belumosudil capsules (administered as two 100-mg capsules) in the fed state

Drug: Belumosudil Capsule

Interventions

Belumosudil Tablet DRUG

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

Regimen A; Regimen B

Belumosudil Capsule DRUG

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

Regimen C

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• To be eligible for study entry subjects has to satisfy all of the following criteria:
• Healthy males
• Aged 18 to 55 years of age
• 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)
• Body mass index 18.0-30.0 kg/m\^2, or if outside the range, considered not clinically significant by the Investigator
• Willing and able to communicate and participate in the whole study
• Provide written informed consent
• Agree to use an adequate method of contraception for up to 90 days post discharge

You may not qualify if:

• Subjects are excluded from the study if one of more of the following statements is applicable:
• Participated in a clinical research study within the previous 3 months
• Study site employees, or immediate family members of a study site or sponsor employee
• Had been previously enrolled in this study
• History of any drug or alcohol abuse in the past 2 years
• Regular alcohol consumption \> 21 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine)
• 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
• Did not have suitable veins for multiple venepunctures/cannulation as assessed by the Investigator at screening
• Clinically significant abnormal biochemistry, hematology, coagulation, or urinalysis as judged by the Investigator
• Positive drugs of abuse test result or alcohol breath test
• Positive hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody (Ab) or human immunodeficiency virus (HIV) results
• 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
• 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

Sponsors & Collaborators

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

Study Sites (1)

Quotient Clinical Limited

Ruddington Nottingham, NG116JS, United Kingdom

Location

Related Publications (1)

• Schueller O, McDermott J, Evans P, Lohmer L, Alabanza A, Patel J. Phase 1 Studies to Evaluate the Food Effect and Relative Bioavailability of Tablet and Capsule Formulations of Belumosudil in Healthy Adult Subjects. Clin Pharmacol Drug Dev. 2022 Jul;11(7):807-814. doi: 10.1002/cpdd.1083. Epub 2022 Mar 2.

  PMID: 35238174 BACKGROUND

MeSH Terms

Interventions

belumosudil

Results Point of Contact

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

olivier.schueller@kadmon.com

833-900-5366

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2015
• First Posted: September 23, 2015
• Study Start: September 1, 2015
• Primary Completion: October 12, 2015
• Study Completion: October 12, 2015
• Last Updated: May 25, 2022
• Results First Posted: October 20, 2021

Record last verified: 2022-05

Locations

GB (1)