A Study to Evaluate How Well Single and Multiple Doses of GLPG3121-modified Release Formulation Are Tolerated in Healthy, Adult Subjects

Study Overview
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Brief Summary
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The aim of the study is to examine the safety and tolerability of GLPG3121-modified release formulation when given to healthy male subjects once as a single dose or multiple times over a period of 14 days in fasting condition or after a standard breakfast. The study will evaluate how the body absorbs and breaks down GLPG3121, and how GLPG3121 and the major breakdown product of GLPG3121 are eliminated from the body. In addition, the study will investigate the effect of food (high-fat) after a single oral dose of GLPG3121 as modified release tablet.

Official Title
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A Phase I, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Oral Doses of GLPG3121-modified Release Formulation in Adult, Healthy, Male Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: GLPG3121
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male between 18 and 55 years of age (extremes included), on the date of signing the informed consent form (ICF). 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, 12-lead electrocardiogram (ECG), and fasting clinical laboratory safety tests, available at screening and prior to randomization. Hemoglobin, neutrophil, lymphocyte, and platelet counts must be above the lower limit of normal range. Total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and serum creatinine 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. Subject must be able and willing to comply with restrictions on prior and concomitant medication. Negative screen for drugs (amphetamines, barbiturates, benzodiazepines, cannabis, cocaine, opiates, methadone, tricyclic antidepressants) and alcohol. This list only contains the key inclusion criteria. Exclusion Criteria: Known hypersensitivity to investigational product (IP) ingredients or history of a significant allergic reaction to IP 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 the IP. 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 the IP. 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. This list only contains the key exclusion criteria.

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

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Part 1 Single Ascending Dose (SAD) and Part 2 Multiple Ascending Dose (MAD) are randomized, double-blind, placebo-controlled; Part 3 Food-effect (FE) is randomized, open-label, crossover
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GLPG3121 SAD<br>Single doses of GLPG3121 at up to 3 dose levels in ascending order | Drug: GLPG3121<br>* GLPG3121 modified-release tablet<br>|
| Placebo Comparator: Placebo SAD<br>Single doses of placebo | Drug: Placebo<br>* Matching placebo<br>|
| Experimental: GLPG3121 MAD<br>Multiple doses of GLPG3121 at up to 3 dose levels in ascending order | Drug: GLPG3121<br>* GLPG3121 modified-release tablet<br>|
| Placebo Comparator: Placebo MAD<br>Multiple doses of placebo | Drug: Placebo<br>* Matching placebo<br>|
| Experimental: GLPG3121 FE fed<br>Single dose of GLPG3121 in fed state | Drug: GLPG3121<br>* GLPG3121 modified-release tablet<br>|
| Experimental: GLPG3121 FE fasted<br>Single dose of GLPG3121 in fasted state | Drug: GLPG3121<br>* GLPG3121 modified-release tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and severity of treatment emergent adverse events (TEAEs), treatment-emergent serious adverse events, and TEAEs leading to treatment discontinuations | To evaluate the safety and tolerability of single and multiple ascending oral doses of GLPG3121-modified-release formulation (GLPG3121-MR), in adult, healthy, male subjects compared with placebo | From screening through study completion, an average of 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration (Cmax) of GLPG3121 in SAD | To evaluate the pharmacokinetics (PK) of single ascending oral doses of GLPG3121 in adult, healthy, male subjects | Between Day 1 pre-dose and Day 6 | 
| Cmax of GLPG3121's main metabolite in SAD | To evaluate the PK of single ascending oral doses of GLPG3121's metabolite in adult, healthy, male subjects | Between Day 1 pre-dose and Day 6 | 
| Cmax of GLPG3121 in MAD | To evaluate the PK of multiple ascending oral doses of GLPG3121 in adult, healthy, male subjects | Between Day 1 pre-dose and Day 19 | 
| Cmax of GLPG3121's main metabolite in MAD | To evaluate the PK of multiple ascending oral doses of GLPG3121's main metabolite in adult, healthy, male subjects | Between Day 1 pre-dose and Day 19 | 
| Area under the plasma concentration-time curve (AUC) of GLPG3121 in SAD | To evaluate the PK of single ascending oral doses of GLPG3121 in adult, healthy, male subjects | Between Day 1 pre-dose and Day 6 | 
| AUC of GLPG3121's main metabolite in SAD | To evaluate the PK of single ascending oral doses of GLPG3121's main metabolite in adult, healthy, male subjects | Between Day 1 pre-dose and Day 6 | 
| AUC of GLPG3121 in MAD | To evaluate the PK of multiple ascending oral doses of GLPG3121 metabolite in adult, healthy, male subjects | Between Day 1 pre-dose and Day 19 | 
| AUC of GLPG3121's main metabolite in MAD | To evaluate the PK of multiple ascending oral doses of GLPG3121's main metabolite in adult, healthy, male subjects | Between Day 1 pre-dose and Day 19 | 
| Terminal elimination half-life (t1/2) of GLPG3121 in SAD | To evaluate the PK of single ascending oral doses of GLPG3121 in adult, healthy, male subjects | Between Day 1 pre-dose and Day 6 | 
| t1/2 of GLPG3121's main metabolite in SAD | To evaluate the PK of single ascending oral doses of GLPG3121's main metabolite in adult, healthy, male subjects | Between Day 1 pre-dose and Day 6 | 
| t1/2 of GLPG3121 in MAD | To evaluate the PK of multiple ascending oral doses of GLPG3121 in adult, healthy, male subjects | Between Day 1 pre-dose and Day 19 | 
| t1/2 of GLPG3121's main metabolite in MAD | To evaluate the PK of multiple ascending oral doses of GLPG3121's main metabolite in adult, healthy, male subjects | Between Day 1 pre-dose and Day 19 |