A Study to Determine the Effect of Multiple Oral Doses and Regimens of KD025 in Healthy Male and Post-menopausal Female Subjects

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety, tolerability, and pharmacokinetics of multiple oral doses and regimens of KD025 in healthy male and post-menopausal female participants.

Detailed Description
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Up to approximately 37 days including safety follow up period of 30 days after participant is treated with the last dose of study drug.

Official Title
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A Phase 1, Placebo-Controlled, Double-Blind, Dose-Escalating Study to Examine the Safety and Tolerability of Multiple Doses of KD025 (Formerly Called SLX-2119) in Healthy Male and Post- Menopausal Female Subjects

Conditions
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Immune System Disorder (Healthy Volunteer)

Intervention / Treatment
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* Drug: Belumosudil mesylate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy participants between the ages of 18 and 55 years, inclusive. Female who was not of reproductive potential. Able to provide written informed consent prior to the performance of any study specific procedures. Body mass index (BMI) range of 19-30 kilogram per square meter (kg/m2), inclusive. Exclusion Criteria: Past or present disease that is judged by the investigator to have the potential to interfere with the study procedures, compromise safety, or affect the PK evaluations. Known sensitivity to Rho-associated coiled-coil containing serine/threonine protein kinases (ROCK2) inhibitor agents or to any of the constituents of the KD025 formulation. 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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All

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: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>500 mg KD025 or placebo once daily (QD) for 7 days | Drug: Belumosudil mesylate<br>* Pharmaceutical form: capsule; Route of administration: oral<br>* Other names: SAR445761;Drug: Placebo<br>* Pharmaceutical form: capsule; Route of administration: oral<br>|
| Experimental: Cohort 2<br>800 mg KD025 or placebo QD for 7 days | Drug: Belumosudil mesylate<br>* Pharmaceutical form: capsule; Route of administration: oral<br>* Other names: SAR445761;Drug: Placebo<br>* Pharmaceutical form: capsule; Route of administration: oral<br>|
| Experimental: Cohort 3<br>500 mg KD025 or placebo twice daily (BID) for 7 days | Drug: Belumosudil mesylate<br>* Pharmaceutical form: capsule; Route of administration: oral<br>* Other names: SAR445761;Drug: Placebo<br>* Pharmaceutical form: capsule; Route of administration: oral<br>|
| Experimental: Cohort 4<br>1000 mg KD025 or placebo QD for 7 days | Drug: Belumosudil mesylate<br>* Pharmaceutical form: capsule; Route of administration: oral<br>* Other names: SAR445761;Drug: Placebo<br>* Pharmaceutical form: capsule; Route of administration: oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events and serious adverse events | Safety observations and measurements include AEs, safety laboratory tests, vital sign measurements, physical examinations, and ECGs. | Up to approximately 37 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of KD025 and its metabolites [M1 (KD025m1) and M2 (KD025m2)] | Cmax is maximum plasma concentration determined directly from the concentration time profile | Predose and multiple timepoints up to 48 hours postdose on Days 1 and 7 | 
| tmax of KD025 and its metabolites [M1 (KD025m1) and M2 (KD025m2)] | tmax is observed time to reach peak plasma concentration | Predose and multiple timepoints up to 48 hours postdose on Days 1 and 7 | 
| AUC0-24 of KD025 and its metabolites [M1 (KD025m1) and M2 (KD025m2)] | AUC0-24 is area under the plasma concentration-time curve from predose (time 0) to 24 hours Postdose | Predose and multiple timepoints up to 48 hours postdose on Days 1 and 7 | 
| AUCinf of KD025 and its metabolites [M1 (KD025m1) and M2 (KD025m2)] | AUCinf is area under the concentration-time curve from predose (time 0) extrapolated to Infinity | Predose and multiple timepoints up to 48 hours postdose on Days 1 and 7 | 
| Cmin of KD025 and its metabolites [M1 (KD025m1) and M2 (KD025m2)] | Cmin is minimum or trough plasma concentration after its administration and just prior to the administration of a subsequent dose as determined from the concentration time profile | Predose and multiple timepoints up to 48 hours postdose on Days 1 and 7 | 
| t1/2 of KD025 and its metabolites [M1 (KD025m1) and M2 (KD025m2)] | t1/2 is terminal elimination half-life | Predose and multiple timepoints up to 48 hours postdose on Days 1 and 7 |