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

Rheumatoid Arthritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04608344
• Other study ID #: GS-US-417-5937
• Status: Completed
• Phase: Phase 1
• Start date: November 4, 2020
• Est. completion date: January 13, 2021

Study information

• Verified date: May 2022
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: January 13, 2021
• Est. primary completion date: January 13, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Atorvastatin
Administered as single dose tablet orally.
• Pravastatin
Administered as single dose tablet orally.
• Rosuvastatin
Administered as single dose tablet orally.
• Filgotinib
Administered as tablet orally once daily for 11 days.

Locations

Country	Name	City	State
United States	Prism Research, LLC	Saint Paul	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Gilead Sciences	Galapagos NV

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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