Drug-drug Interaction Study With GLPG3970 and Sulfasalazine in Adult, Healthy Subjects

Study Overview
=================
Brief Summary
-----------------
GLPG3970 will be given with sulfasalazine to investigate the effect of co-administration on the pharmacokinetics of sulfasalazine, and on the safety and tolerability of the drugs in healthy adult subjects.

Official Title
-----------------
A Phase 1, Fixed Sequence, Open-label, Drug-drug Interaction Study to Evaluate the Effect of GLPG3970 on the Pharmacokinetics of Sulfasalazine in Adult, Healthy Subjects

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: Sulfasalazine
* Drug: GLPG3970


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female between 18 and 55 years of age (extremes included), on the date of signing the informed consent form (ICF). Females should be of non-childbearing potential. A body mass index (BMI) between 18.0 to 30.0 kg/m2, inclusive. A breast cancer resistance protein (BCRP) c421C/C genotype. Judged to be in good health by the investigator based upon the results of a medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG), and fasting clinical laboratory safety tests, available at screening and prior to the first sulfasalazine administration. Bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) must be no greater than 1.5x upper limit of normal range (ULN). Other clinical laboratory safety test results must be within the reference ranges or test results that are outside the reference ranges need to be considered not clinically significant in the opinion of the investigator. This list only contains the key inclusion criteria. Exclusion Criteria: Known hypersensitivity to the investigational product (IP) (GLPG3970), or sulfasalazine, or sulfa drugs, or to their ingredients, or history of a significant allergic reaction to IP or sulfasalazine ingredients as determined by the investigator. Positive serology for hepatitis B virus surface antigen (HBsAg) or hepatitis C virus (HCV) or history of hepatitis from any cause with the exception of hepatitis A that was resolved at least 3 months prior to first dosing of sulfasalazine. History of or a current immunosuppressive condition (e.g. human immunodeficiency virus (HIV) infection). Having any illness, judged by the investigator as clinically significant, in the 3 months prior to first dosing of sulfasalazine. Presence or sequelae of gastrointestinal, liver, kidney (estimated glomerular filtration rate (eGFR) <=90 mL/min/1.73 m2, using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula) or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs. Subjects with an N-acetyltransferase 2 (NAT2) slow acetylator genotype. This list only contains the key exclusion criteria.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sulfasalazine + GLPG3970<br> | Drug: Sulfasalazine<br>* On Day 1, Day 5 and Day 9, a single oral dose of sulfasalazine tablets in fasted state.<br>Drug: GLPG3970<br>* On Day 5 and Day 9, a single dose of GLPG3970 oral solution in fasted state.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed concentration (Cmax) of sulfasalazine | To evaluate the effect of GLPG3970 on the pharmacokinetics (PK) of sulfasalazine and its active metabolite sulfapyridine in healthy subjects. | Between Day 1 pre-dose and Day 12 | 
| Cmax of sulfapyridine | To evaluate the effect of GLPG3970 on the pharmacokinetics (PK) of sulfasalazine and its active metabolite sulfapyridine in healthy subjects. | Between Day 1 pre-dose and Day 12 | 
| Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) of sulfasalazine | To evaluate the effect of GLPG3970 on the pharmacokinetics (PK) of sulfasalazine and its active metabolite sulfapyridine in healthy subjects. | Between Day 1 pre-dose and Day 12 | 
| AUC0-inf of sulfapyridine | To evaluate the effect of GLPG3970 on the pharmacokinetics (PK) of sulfasalazine and its active metabolite sulfapyridine in healthy subjects. | Between Day 1 pre-dose and Day 12 | 
| Sulfapyridine to sulfasalazine AUC ratio | To evaluate the effect of GLPG3970 on the pharmacokinetics (PK) of sulfasalazine and its active metabolite sulfapyridine in healthy subjects. | Between Day 1 pre-dose and Day 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Treatment-emergent Adverse Events (TEAEs) by Severity | To evaluate the safety and tolerability of the coadministration of GLPG3970 with sulfasalazine in healthy subjects | From Day 1 through study completion, an average of 1 month | 
| Maximum observed concentration (Cmax) of GLPG3970 | To evaluate the PK of GLPG3970 in presence of sulfasalazine in healthy subjects | Between Day 5 pre-dose and Day 10 | 
| Area under the plasma concentration-time curve from time zero till the last observed quantifiable concentration (AUC0-t) | To evaluate the PK of GLPG3970 in presence of sulfasalazine in healthy subjects | Between Day 5 pre-dose and Day 10 |