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

Primary Purpose

Rheumatoid Arthritis

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Atorvastatin
Pravastatin
Rosuvastatin
Filgotinib
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Rheumatoid Arthritis

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Prism Research, LLC

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Sequence AB

Sequence BA

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.
PK Parameter: AUCinf of ATV, PRA, and ROS
AUCinf is defined as the concentration of drug extrapolated to infinite time.
PK Parameter: Cmax of ATV, PRA, and ROS
Cmax is defined as the maximum observed concentration of drug.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
October 23, 2020
Last Updated
May 26, 2022
Sponsor
Gilead Sciences
Collaborators
Galapagos NV
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1. Study Identification

Unique Protocol Identification Number
NCT04608344
Brief Title
Study to Evaluate Organic Anion Transporting Polypeptide (OATP) Transporter-Mediated Drug-Drug Interactions Between Filgotinib and Statins as Probe Drugs in Healthy Participants
Official Title
A Phase 1 Study to Evaluate OATP Transporter-Mediated Drug-Drug Interactions Between Filgotinib and Statins as Probe Drugs in Healthy Participants
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
November 4, 2020 (Actual)
Primary Completion Date
January 13, 2021 (Actual)
Study Completion Date
January 13, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
Collaborators
Galapagos NV

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sequence AB
Arm Type
Experimental
Arm Description
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.
Arm Title
Sequence BA
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Atorvastatin
Intervention Description
Administered as single dose tablet orally.
Intervention Type
Drug
Intervention Name(s)
Pravastatin
Intervention Description
Administered as single dose tablet orally.
Intervention Type
Drug
Intervention Name(s)
Rosuvastatin
Intervention Description
Administered as single dose tablet orally.
Intervention Type
Drug
Intervention Name(s)
Filgotinib
Other Intervention Name(s)
GS-6034, GLPG0634, Jyseleca
Intervention Description
Administered as tablet orally once daily for 11 days.
Primary Outcome Measure Information:
Title
Pharmacokinetic (PK) Parameter: AUClast of ATV, PRA, and ROS
Description
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Time Frame
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
Title
PK Parameter: AUCinf of ATV, PRA, and ROS
Description
AUCinf is defined as the concentration of drug extrapolated to infinite time.
Time Frame
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
Title
PK Parameter: Cmax of ATV, PRA, and ROS
Description
Cmax is defined as the maximum observed concentration of drug.
Time Frame
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 Measure Information:
Title
Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)
Description
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.
Time Frame
Sequence AB: First dose up to 47 days, Sequence BA: First dose up to 50 days
Title
Percentage of Participants With Severity Grade 3 or Above Treatment-Emergent Laboratory Abnormalities
Description
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.
Time Frame
Sequence AB: First dose up to 47 days, Sequence BA: First dose up to 50 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Prism Research, LLC
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55114
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 URL
https://www.gileadclinicaltrials.com/transparency-policy/

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

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