Study to Evaluate Organic Anion Transporting Polypeptide (OATP) Transporter-Mediated Drug-Drug Interactions Between Filgotinib and Statins as Probe Drugs in Healthy Participants

A Phase 1 Study to Evaluate OATP Transporter-Mediated Drug-Drug Interactions Between Filgotinib and Statins as Probe Drugs in Healthy Participants

The primary objective of this study is to evaluate the effect of filgotinib on a mixed organic anion transporting polypeptide/cytochrome P450 3A (OATP/CYP3A), OATP/ breast cancer resistance protein (BCRP), and OATP substrates using phenotypic probes.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Atorvastatin; Drug: Pravastatin; Drug: Rosuvastatin; Drug: Filgotinib

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Prism research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Be a nonsmoker. The use of nicotine or nicotine-containing products must be discontinued 90 days prior to the first dose of study drug.
• Have a calculated body mass index (BMI) of greater than or equal to (≥) 19.0 and less than or equal to (≤) 30.0 kilogram per meter square (kg/m^2) at screening.
• Have a creatinine clearance (CLcr) ≥ 90 milliliters per minute (mL/min) (using the Cockcroft-Gault method) based on serum creatinine and actual body weight as measured at screening and upon admission.
• Female participants of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at clinic admission.
• Male participants must be surgically sterile.
• Male participants and female participants of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.
• Screening laboratory evaluations and 12-lead electrocardiogram (ECG) evaluations must be without clinically significant abnormalities as assessed by the investigator.
• Have liver biometric tests such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and total bilirubin below the upper limit of normal at screening.
• Must be willing and able to comply with all study requirements.
• Must, in the opinion of the investigator, be in good health based upon medical history and physical examination, including vital signs.
• Participants must not have donated blood within 56 days of study entry or plasma within 7 days of study entry and must refrain from blood donation from clinic admission, throughout the study period, and continuing for at least 30 days following the last dose of study drug.

Key Exclusion Criteria:

• Positive serum pregnancy test (Female participants).
• Lactating female.
• Have received any investigational drug/device within 30 days prior to study dosing (or within 5 half-lives of the drug, whichever is longer).
• Have current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance or participant safety, or a positive drug or alcohol test at screening or admission.
• Have a positive test result for human immunodeficiency virus type 1 (HIV-1) antibody, hepatitis B virus (HBV) surface antigen (HBsAg), or hepatitis C virus (HCV) antibody at screening.
• Have positive Coronavirus Disease 2019 (COVID-19) Real-Time Reverse.
• Transcriptase-Polymerase Chain Reaction (RT-PCR) testing on screening and admission.
• Have poor venous access that limits phlebotomy.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence AB; Participants will receive atorvastatin (ATV) 40 mg tablet on Day 1, followed by a washout period of 1 day, and then pravastatin (PRA) 40 mg + rosuvastatin (ROS) 10 mg tablets on Day 3 in Treatment A, Period 1. In Treatment B, Period 2 participants will receive filgotinib 200 mg tablet once daily for 11 days, with ATV 40 mg on Day 12 and PRA 40 mg + ROS 10 mg tablets on Day 14. Period 1 and Period 2 will be separated by a washout period of 3 days.	Drug: Atorvastatin; Administered as single dose tablet orally.; Drug: Pravastatin; Administered as single dose tablet orally.; Drug: Rosuvastatin; Administered as single dose tablet orally.; Drug: Filgotinib; Administered as tablet orally once daily for 11 days.; Other Names: GS-6034; GLPG0634; Jyseleca
Experimental: Sequence BA; Participants will receive filgotinib 200 mg tablet once daily for 11 days, with ATV 40 mg on Day 6 and PRA 40 mg + ROS 10 mg tablets on Day 8 in Treatment B, Period 1. In Treatment A, Period 2 participants will receive ATV 40 mg tablet on Day 18, followed by a washout period of 1 day and PRA 40 mg + ROS 10 mg tablets on Day 20. Period 1 and Period 2 will be separated by a washout period of 6 days.	Drug: Atorvastatin; Administered as single dose tablet orally.; Drug: Pravastatin; Administered as single dose tablet orally.; Drug: Rosuvastatin; Administered as single dose tablet orally.; Drug: Filgotinib; Administered as tablet orally once daily for 11 days.; Other Names: GS-6034; GLPG0634; Jyseleca

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) Parameter: AUClast of ATV, PRA, and ROS	AUClast is defined as the concentration of drug from time zero to the last observable concentration.	AB (Days 1,3,12,14) and BA (Days 6,8,18,20): Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 postdose; AB (Days 1,12) and BA (Days 6,18): 5,10,36 hours post dose; AB (Days 3,14) and BA (Days 8,20): 72 hours postdose
PK Parameter: AUCinf of ATV, PRA, and ROS	AUCinf is defined as the concentration of drug extrapolated to infinite time.	AB (Days 1,3,12,14) and BA (Days 6,8,18,20): Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 postdose; AB (Days 1,12) and BA (Days 6,18): 5,10,36 hours post dose; AB (Days 3,14) and BA (Days 8,20): 72 hours postdose
PK Parameter: Cmax of ATV, PRA, and ROS	Cmax is defined as the maximum observed concentration of drug.	AB (Days 1,3,12,14) and BA (Days 6,8,18,20): Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 postdose; AB (Days 1,12) and BA (Days 6,18): 5,10,36 hours post dose; AB (Days 3,14) and BA (Days 8,20): 72 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a participant administered a study drug, which did not necessarily have a causal relationship with the treatment. AE was therefore any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of the study drug, whether or not considered related to the study drug. TEAEs: AE with an onset date on or after the study drug start date and no later than 30 days after study drug stop date; or any AE leading to study drug discontinuation.	Sequence AB: First dose up to 47 days, Sequence BA: First dose up to 50 days
Percentage of Participants With Severity Grade 3 or Above Treatment-Emergent Laboratory Abnormalities	Treatment-emergent laboratory abnormalities were graded using Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 of Adverse Events and Laboratory abnormalities. Laboratory abnormalities were graded as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (Life-threatening), Grade 5 (Death). Percentage of participants with Grade 3 or higher treatment-emergent laboratory abnormalities were reported.	Sequence AB: First dose up to 47 days, Sequence BA: First dose up to 50 days

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Collaborators: Galapagos NV

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2020
• Primary Completion (Actual): January 13, 2021
• Study Completion (Actual): January 13, 2021

Study Registration Dates

• First Submitted: October 23, 2020
• First Submitted That Met QC Criteria: October 23, 2020
• First Posted (Actual): October 29, 2020

Study Record Updates

• Last Update Posted (Actual): June 14, 2022
• Last Update Submitted That Met QC Criteria: May 26, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Rosuvastatin Calcium; Pravastatin
• Other Study ID Numbers: GS-US-417-5937

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gileadclinicaltrials.com/transparency-policy/
• IPD Sharing Time Frame: 18 months after study completion
• IPD Sharing Access Criteria: A secured external environment with username, password, and RSA code.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No