Drug-Drug Interaction Study to Investigate Effects of Voclosporin on Pharmacokinetics of Simvastatin

Study Overview
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Brief Summary
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A single-center, open-label, Phase 1, drug-drug interaction study to investigate the effect of voclosporin on the pharmacokinetics of simvastatin and simvastatin acid in healthy volunteers.

Official Title
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A Single Center, Open Label, Phase 1 Drug-Drug Interaction Study to Investigate the Effects of Voclosporin on the Pharmacokinetics of Simvastatin in Healthy Volunteers

Conditions
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Drug-drug Interaction

Intervention / Treatment
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* Drug: Simvastatin
* Drug: Voclosporin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Healthy male or female subjects aged >=18 and <=55 years Body mass index >=18.0 and <32 kg/m2 Exclusion Criteria: Abnormal ECG and/or prolonged QT interval Subjects using nicotine products within 3 months prior to screening Subjects who have lost or donated >450 mL of whole blood or blood products within 30 days prior to the Screening Visit. Use of any prescription medication within 14 days prior to the first dose of study medication, or any over-the-counter products (including natural health products, e.g., food supplements, vitamins, herbal supplements) within 7 days prior to the first dose of study medication, except for topical products without significant systemic absorption. Use of any drugs or substances known to induce or inhibit hepatic drug metabolism within 28 days prior to administration of the study medication Consumption of grapefruit or grapefruit juice, pomelo or star fruit within 7 days of first dose of study drug on Day 1 Use of hormonal contraception or hormone replacement therapy within 14 days prior to first dose of study drug. No COVID-19 vaccines are allowed within 28 days prior to first dose of study drug. History of or current alcohol abuse or drug addiction Subjects who are pregnant or breast feeding Subjects who have received any investigational drug within 30 days or 5 half-lives of the drug (whichever is longer) prior to screening. Subjects who have any significant health issues as deemed by their treating physician/investigator

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: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Voclosporin/Simvastatin<br>Subjects will receive a single oral dose of 40 mg simvastatin (given as two 20 mg tablets) in the morning of Day 1 and Day 8. Subjects will receive voclosporin administered as an oral 23.7 mg dose (three 7.9 mg capsules) twice-daily for 7 days from the morning of Day 2 until the evening of Day 8. | Drug: Simvastatin<br>* Oral dose 40 mg<br>Drug: Voclosporin<br>* Oral dose 23.7 mg twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of simvastatin and simvastatin acid (Cmax) | To evaluate the potential effect of multiple oral doses of voclosporin on the single-dose PK of simvastatin and the active metabolite simvastatin acid. Maximum observed concentration (Cmax). | 9 days | 
| Pharmacokinetics of simvastatin and simvastatin acid (AUC) | To evaluate the potential effect of multiple oral doses of voclosporin on the single-dose PK of simvastatin and the active metabolite simvastatin acid. Area under the concentration-time curve (AUC) from time zero to infinity. | 9 days | 
| Pharmacokinetics of simvastatin and simvastatin acid (AUC) | To evaluate the potential effect of multiple oral doses of voclosporin on the single-dose PK of simvastatin and the active metabolite simvastatin acid. Area under the concentration-time curve (AUC) time zero to last quantifiable concentration. | 9 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of voclosporin (Cmax) | To evaluate voclosporin blood concentrations - Cmax. | 9 days | 
| Pharmacokinetics of voclosporin (AUC) | To evaluate voclosporin blood concentrations - AUC from time zero to 12 hours. | 9 days | 
| Pharmacokinetics of voclosporin (Tmax) | To evaluate voclosporin blood concentrations - Time to reach maximum observed plasma concentration (Tmax). | 9 days | 
| Pharmacokinetics of voclosporin (Ctrough) | To evaluate voclosporin blood concentrations - Trough concentration (Ctrough) at the end of a dosing interval at steady state. | 9 days | 
| Pharmacokinetics of voclosporin (CL/F) | To evaluate voclosporin blood concentrations - apparent clearance (CL/F). | 9 days | 
| Number of participants with abnormal laboratory test results | Number of subjects with abnormal laboratory test results (eg., hematology, biochemistry and urinalysis) will be assessed | Up to 2 weeks | 
| Number of participants with abnormal vital signs | Number of participants with abnormal vital signs (eg., blood pressure, heart rate, body temperature, respiratory rate) will be assessed | Up to 2 weeks | 
| 12-Lead Electrocardiogram Assessment | Standard 12-lead electrocardiograms (eg., QTcF interval) will be summarized by observed value and change from baseline values. | Up to 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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voclosporin, simvastatin, pharmacokinetics, drug effects, drug interactions