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

NCT04608344 | Completed Phase 1 Results FDA Drug

• 1 other identifier: GS-US-417-5937
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)

  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

  Sequence AB: First dose up to 47 days, Sequence BA: First dose up to 50 days

Study Arms (2)

Sequence AB

EXPERIMENTAL

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; Drug: Pravastatin; Drug: Rosuvastatin; Drug: Filgotinib

Sequence BA

EXPERIMENTAL

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; Drug: Pravastatin; Drug: Rosuvastatin; Drug: Filgotinib

Interventions

Atorvastatin DRUG

Administered as single dose tablet orally.

Sequence AB; Sequence BA

Pravastatin DRUG

Administered as single dose tablet orally.

Sequence AB; Sequence BA

Rosuvastatin DRUG

Administered as single dose tablet orally.

Sequence AB; Sequence BA

Filgotinib DRUG

Administered as tablet orally once daily for 11 days.

Also known as: GS-6034, GLPG0634, Jyseleca

Sequence AB; Sequence BA

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead
• Galapagos NV: collaborator

Study Sites (1)

Prism Research, LLC

Saint Paul, Minnesota, 55114, United States

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Atorvastatin; Pravastatin; Rosuvastatin Calcium; GLPG0634

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Sulfonamides; Amides; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Sulfones; Sulfur Compounds; Pyrimidines

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2020
• First Posted: October 29, 2020
• Study Start: November 4, 2020
• Primary Completion: January 13, 2021
• Study Completion: January 13, 2021
• Last Updated: June 14, 2022
• Results First Posted: January 19, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.

Locations

US (1)