Drug-Drug Interaction Study to Investigate Effects of Voclosporin on Pharmacokinetics of Simvastatin (Statin-DDI)

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

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.

Study Overview

• Status: Completed
• Conditions: Drug-drug Interaction
• Intervention / Treatment: Drug: Simvastatin; Drug: Voclosporin

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • Labcorp Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Voclosporin/Simvastatin; 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; Oral dose 40 mg; Drug: Voclosporin; Oral dose 23.7 mg twice daily

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Aurinia Pharmaceuticals Inc.
• Investigators: Study Director: Winnie Lim, Aurinia Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2022
• Primary Completion (Actual): April 5, 2022
• Study Completion (Actual): April 5, 2022

Study Registration Dates

• First Submitted: February 7, 2022
• First Submitted That Met QC Criteria: March 23, 2022
• First Posted (Actual): April 1, 2022

Study Record Updates

• Last Update Posted (Actual): April 20, 2022
• Last Update Submitted That Met QC Criteria: April 19, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: pharmacokinetics; drug effects; voclosporin; simvastatin; drug interactions
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: AUR-VCS-2021-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No