A Study to Assess the Effect of Oral Belumosudil on Inhibition of Various Proteins in the Fed State in Healthy Male Subjects

Study Overview
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Brief Summary
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The purpose of this study is to evaluate safety and pharmacokinetics (PK) effect of belumosudil on the uridine diphosphate glucuronosyltransferase (UGT)1A1 (Part 1), P glycoprotein (P-gp) (Part 2) and breast cancer resistance protein (BCRP)/organic anion transporting polypeptide (OATP)1B1 (Part 3) inhibition in the fed state in healthy male subjects.

Detailed Description
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Part 1: The estimated time from screening until the follow-up phone call is approximately 6 weeks per subject. Part 2: The estimated time from screening until the follow-up phone call is approximately 7 weeks per subject. Part 3: The estimated time from screening until the follow-up phone call is approximately 7 weeks per subjects.

Official Title
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A Three-part, Sequential, Non-randomized, Open-label Study Designed to Evaluate the Effect of Oral Belumosudil on UGT1A1, P-gp, BCRP and OATP1B1 Inhibition in the Fed State in Healthy Male Subjects

Conditions
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Immune System Disorder (Healthy Volunteers)

Intervention / Treatment
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* Drug: Belumosudil
* Drug: UGT1A1 victim drug
* Drug: P-gp victim drug
* Drug: OATP1B1/BCRP victim drug


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male participants aged 18 to 55 years old Must agree to use an adequate method of contraception Must be able to understand and provide a written informed consent Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active. Significant serious skin disease, including rash, food allergy, eczema, psoriasis, or urticaria. Failure to satisfy the investigator of fitness to participate for any other reason. The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1<br>Belumosudil + UGT1A1 victim drug administered in the fed state | Drug: Belumosudil<br>* Pharmaceutical form: Tablet; Route of administration: Oral<br>* Other names: REZUROCK/KD025/SAR445761;Drug: UGT1A1 victim drug<br>* Pharmaceutical form: Tablet; Route of administration: Oral<br>|
| Experimental: Part 2<br>Belumosudil + P-gp victim drug administered in the fed state | Drug: Belumosudil<br>* Pharmaceutical form: Tablet; Route of administration: Oral<br>* Other names: REZUROCK/KD025/SAR445761;Drug: P-gp victim drug<br>* Pharmaceutical form: Capsule; Route of administration: Oral<br>|
| Experimental: Part 3<br>Belumosudil + OATP1B1/BCRP victim drug administered in the fed state | Drug: Belumosudil<br>* Pharmaceutical form: Tablet; Route of administration: Oral<br>* Other names: REZUROCK/KD025/SAR445761;Drug: OATP1B1/BCRP victim drug<br>* Pharmaceutical form: Tablet; Route of administration: Oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC(0-last)- Parts 1,2, and 3 (victim drugs) | Area under the curve from time 0 to the time of last measurable concentration | Multiple timepoints up to approximately 15 days | 
| AUC(0-inf)- Parts 1,2, and 3 (victim drugs | Area under the curve from time 0 extrapolated to infinity | Multiple timepoints up to approximately 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax- Parts 1, 2, and 3 (victim drugs, belumosudil and belumosudil metabolites) | Time of maximum observed concentration. | Multiple timepoints up to approximately 15 days | 
| Cmax -Parts 1, 2, and 3 (victim drugs, belumosudil and belumosudil metabolites) | Maximum observed concentration | Multiple timepoints up to approximately 15 days | 
| T1/2 -Parts 1, 2, and 3 (victim drugs, belumosudil and belumosudil metabolites) | Terminal elimination half-life | Multiple timepoints up to approximately 15 days | 
| AUC(0-last)-Part 1 (victim metabolite) |  | Multiple timepoints up to approximately 10 days | 
| AUC(0-inf)- Part 1 (metabolite of victim drug) |  | Multiple timepoints up to approximately 10 days | 
| Tmax- Part 1(metabolite of victim drug) |  | Multiple timepoints up to approximately 10 days | 
| Cmax- Part 1 (metabolite of victim drug) |  | Multiple timepoints up to approximately 10 days | 
| T1/2- Part 1 (metabolite of victim drug) |  | Multiple timepoints up to approximately 10 days | 
| AUC(0-last) - Parts 1, 2, and 3 (Belumosudil and metabolites) |  | Multiple timepoints up to approximately 15 days | 
| Area under the curve for the defined interval between doses (tau) [AUC(0 tau)] - Parts 1, 2, and 3 | Area under the curve for the defined interval between doses (tau) | Multiple timepoints up to approximately 15 days | 
| Number of participants with adverse events (AEs) and serious adverse events (SAEs) | To provide additional safety and tolerability information for belumosudil by assessing: AEs, vital signs, ECGs, physical examinations and laboratory safety tests following administration of the three victim drugs alone and in combination with belumosudil. | Up to 30 days after the administration of last dose of study drug i.e., up to approximately 43 days |