Drug-drug Interaction Between Belumosudil, Itraconazole, Rifampicin, Rabeprazole, and Omeprazole in Healthy Volunteers

NCT03530995 | Completed Phase 1 Results

• 2 other identifiers: KD025-1072018-000316-16
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, 2-part, non-randomized, open-label study of the drug-drug interactions of belumosudil (KD025) with itraconazole, rifampicin, rabeprazole, and omeprazole in healthy male subjects.

Conditions

Drug-drug Interaction; Autoimmune Diseases; Fibrotic Disease

Outcome Measures

Primary Outcomes (5)

• Pharmacokinetics: Cmax of KD025 and KD025m2 in Part 1

  Maximum concentration (Cmax) of the parent drug, KD025, Metabolite 1 (KD025m1), and Metabolite 2 (KD025m2) for belumosudil alone, belumosudil + itraconazole, belumosudil + rabeprazole, and belumosudil + rifampicin at 0 to 48 hours post-dose

  Pre-dose and 0.5,1,1.5,2,3,4,5,6,8,10,12,24,36, and 48 hours post-dose

• Pharmacokinetics: Cmax of KD025m1 in Part 1

  Maximum concentration (Cmax) of Metabolite 1 (KD025m1) for belumosudil alone and for belumosudil + rifampicin up to 48 hours post-dose

  Pre-dose and 0.5,1,1.5,2,3,4,5,6,8,10,12,24,36, and 48 hours post-dose

• Pharmacokinetics: Cmax of KD025, KD025m1, and KD025m2 in Part 2

  Maximum concentration (Cmax) of the parent drug (KD025), for Metabolite 1 (KD025m1), and for Metabolite 2 (KD025m2), for belumosudil alone and for belumosudil + omeprazole up to 48 hours post-dose

  Pre-dose and 0.5,1,1.5,2,3,4,5,6,8,10,12,12.5,13,13.5,14,15,16,17,18,20,22,24,36, and 48 hours post-dose

• Pharmacokinetics: AUC(0-inf) and AUC(0-24) of KD025 and KD025 m2 for Subject in Part 1 and Part 2

  Area under concentration-time curve from zero hours to infinity (AUC\[0-inf\]) and from zero hours to 24 hours post-dose (AUC\[0-24)) for the parent drug KD025, and Metabolite 2, KD025m2, for subjects up to 48 hours each for Part 1 and for Part 2

  Part 1: Pre-dose and 0.5,1,1.5,2,3,4,5,6,8,10,12,24,36, and 48 hours post-dose; Part 2: Pre-dose and 0.5,1,1.5,2,3,4,5,6,8,10,12,12.5,13,13.5,14,15,16,17,18,20,22,24,36, and 48 hours post-dose

• Pharmacokinetics: AUC(0-24) of KD025m1 for Part 1 and for Part 2

  Area under concentration-time curve from zero hours to 24 hours post-dose (AUC\[0-24\]) for Metabolite 1, KD025m1, for subjects in Part 1 and for subjects in Part 2

  Part 1: Pre-dose and 0.5,1,1.5,2,3,4,5,6,8,10,12, and 24 hours post-dose; Part 2: Pre-dose and 0.5,1,1.5,2,3,4,5,6,8,10,12,12.5,13,13.5,14,15,16,17,18,20,22, and 24 hours post-dose

Study Arms (6)

Part 1, Period 1

EXPERIMENTAL

Drug: Belumosudil. Subjects will receive belumosudil 200 mg single dose on Day 1

Drug: Belumosudil

Part 1, Period 2

EXPERIMENTAL

Drug: Itraconazole. Subjects will receive itraconazole 200 mg QD on Day 1 through Day 7. Drug: Belumosudil. Subjects will receive belumosudil 200 mg + itraconazole 200 mg QD on Day 8 Subjects will receive itraconazole 200 mg QD on Day 9

Drug: Belumosudil; Drug: Itraconazole

Part 1, Period 3

EXPERIMENTAL

Drug: Rabeprazole. Subjects will receive rabeprazole 20 mg BID on Day 1 through Day 3. Drug: Belumosudil. Subjects will receive belumosudil 200 mg + rabeprazole 20 mg QD on Day 4.

Drug: Belumosudil; Drug: Rabeprazole

Part 1, Period 4

EXPERIMENTAL

Drug: Rifampicin. Subjects will receive rifampicin 600 mg QD on Day 1 through Day 9. Drug: Belumosudil. Subjects will receive belumosudil 200 mg on Day 10.

Drug: Belumosudil; Drug: Rifampicin

Part 2, Period 1

EXPERIMENTAL

Drug: Belumosudil. Subjects will receive belumosudil 200 mg BID on Day 1.

Drug: Belumosudil

Part 2, Period 2

EXPERIMENTAL

Drug: Omeprazole. Subjects will receive omeprazole 20 mg QD on Day 1 through Day 3. Drug: Belumosudil. Subjects will receive belumosudil 200 mg BID + omeprazole 20 mg QD on Day 4.

Drug: Belumosudil; Drug: Omeprazole

Interventions

Belumosudil DRUG

Development candidate

Also known as: Rezurock, SLx-2119

Part 1, Period 1; Part 1, Period 2; Part 1, Period 3; Part 1, Period 4; Part 2, Period 1; Part 2, Period 2

Itraconazole DRUG

Perpetrator drug

Part 1, Period 2

Rabeprazole DRUG

Perpetrator drug

Part 1, Period 3

Rifampicin DRUG

Perpetrator drug

Part 1, Period 4

Omeprazole DRUG

Perpetrator drug

Part 2, Period 2

Eligibility Criteria

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

You may qualify if:

• Healthy males
• Age 18 to 55 years
• 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 of 18.0 to 32.0 kg/m\^2 or, if outside the range, considered not clinically significant by the investigator
• Must be willing and able to communicate and participate in the whole study
• Must provide written informed consent
• Must adhere to the contraception requirements

You may not qualify if:

• Subjects who had previously participated in any other investigational study drug trial in which receipt of an IP occurred within 90 days prior to dosing. (Subjects who had previously received belumosudil in Part 1 at least 90 days prior to dosing in Part 2 were eligible to participate.)
• 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
• Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening
• Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the investigator
• Positive drugs of abuse test result at screening and admission
• 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 (CLcr) of \<80 mL/min using the Cockcroft-Gault equation
• History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator
• Subject has a history or presence of any of the following:
• Active gastrointestinal disease requiring therapy

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, Willson A, Singh N, Lohmer L, Alabanza A, Patel J. A Phase 1 Pharmacokinetic Drug Interaction Study of Belumosudil Coadministered With CYP3A4 Inhibitors and Inducers and Proton Pump Inhibitors. Clin Pharmacol Drug Dev. 2022 Jul;11(7):795-806. doi: 10.1002/cpdd.1082. Epub 2022 Mar 1.

  PMID: 35230741 BACKGROUND

MeSH Terms

Conditions

Autoimmune Diseases

Interventions

belumosudil; Itraconazole; Rabeprazole; Rifampin; Omeprazole

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

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

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: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Two-Part, Non-Randomised

Study Record Dates

• First Submitted: April 13, 2018
• First Posted: May 21, 2018
• Study Start: April 9, 2018
• Primary Completion: February 8, 2019
• Study Completion: February 8, 2019
• Last Updated: May 25, 2022
• Results First Posted: September 13, 2021

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)