Drug-drug Interaction Study With GLPG4716 and Nintedanib and Pirfenidone in Healthy Subjects

Study Overview
=================
Brief Summary
-----------------
The main aim of this study is to investigate the possible effect of GLPG4716 on the pharmacokinetics (PK) of pirfenidone and nintedanib. Further aims are to investigate safety and tolerability of GLPG4716 alone or administered simultaneously with pirfenidone or nintedanib.

Official Title
-----------------
An Open-label, Fixed-sequence Drug-drug Interaction Study in Healthy Subjects to Evaluate the Effect of GLPG4716 on the Pharmacokinetics of Nintedanib and Pirfenidone

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

Intervention / Treatment
-----------------
* Drug: Pirfenidone
* Drug: GLPG4716
* Drug: Nintedanib


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). Female subjects should be of non-childbearing potential. A body mass index (BMI) between 18.0 and 30.0 kg/m2, inclusive. Judged to be in good health by the investigator based upon the results of a medical history, physical examination, vital signs, electrocardiogram (ECG), and fasting clinical laboratory safety tests. Aspartate transaminase and alanine aminotransferase must be no greater than the upper limit of normal (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 includes the key inclusion criteria. Exclusion Criteria: Known hypersensitivity to ingredients of GLPG4716, pirfenidone, or nintedanib or history of a significant allergic reaction to ingredients of GLPG4716, pirfenidone, or nintedanib as determined by the investigator. Treatment with any medication (including over-the-counter (OTC) and/or prescription medication, dietary supplements, nutraceuticals, vitamins and/or herbal supplements, and hormonal replacement therapy) except occasional paracetamol (maximum dose of 2 g/day and maximum of 10 g/2 weeks) in the last 2 weeks or 5 half-lives of the drug, whichever is longer, prior to the first dosing. This list only includes 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
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GLPG4716 and pirfenidone<br> | Drug: Pirfenidone<br>* On Days 1 and 13, participants will receive an oral dose of pirfenidone.<br>Drug: GLPG4716<br>* From Day 3 to Day 14, participants will receive GLPG4716 daily.<br>|
| Experimental: GLPG4716 and nintedanib<br> | Drug: GLPG4716<br>* From Day 3 to Day 14, participants will receive GLPG4716 daily.<br>Drug: Nintedanib<br>* On Days 1 and 13, participants will receive an oral dose of nintedanib.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration (Cmax) of pirfenidone | To determine the effect of GLPG4716 on the PK of pirfenidone | From Day 1 pre-dose until Day 15 | 
| Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) of pirfenidone | To determine the effect of GLPG4716 on the PK of pirfenidone | From Day 1 pre-dose until Day 15 | 
| Cmax of nintedanib | To determine the effect of GLPG4716 on the PK of nintedanib. | From Day 1 pre-dose until Day 15 | 
| AUC0-inf of nintedanib | To determine the effect of GLPG4716 on the PK of nintedanib. | From Day 1 pre-dose until Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and severity of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (SAEs), and TEAEs leading to treatment discontinuations. | To evaluate the safety and tolerability of GLPG4716 alone or when co-administered with pirfenidone or nintedanib. | From Day 1 through study completion, an average of 2 months |