A Study to Evaluate the Effects of Single and Multiple Oral Doses of GLPG3667

Study Overview
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Brief Summary
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This study is a first-in-human, Phase I, randomized, double-blind, placebo-controlled, single-center, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of GLPG3667 after oral single ascending doses (SAD) of GLPG3667 (part 1) and after oral multiple ascending doses (MAD) for 13 days of GLPG3667 (part 2) in healthy male subjects. In addition, the effect of food (FE) on safety, tolerability, and PK of GLPG3667 oral suspension will be evaluated (part 3 - will not be completed), and the relative bioavailability (rBA) of the capsule versus the oral suspension with the effect of food on the bioavailability of the capsule (part 4), both part 3 and 4 using an open-label, randomized, crossover design.

Official Title
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A First-in-human Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Oral Doses of GLPG3667 in Adult, Healthy, Male Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: GLPG3667 oral suspension
* Drug: Placebos
* Drug: GLPG3667 capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male between 18-55 years of age (extremes included), on the date of signing the informed consent form (ICF) A body mass index (BMI) between 18-30 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. Bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) must be within normal ranges. 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 Exclusion Criteria: Known hypersensitivity to Investigational Medicinal Product (IMP) ingredients or history of a significant allergic reaction to IMP ingredients as determined by the investigator Known contraindication or hypersensitivity to Interferon-alpha (IFN-α) or any component of Intron-A® (Note: this criterion is only applicable to subjects in the MAD part) 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 IMP.

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: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GLPG3667 SAD<br>Single doses of GLPG3667 at up to 6 dose levels in ascending order | Drug: GLPG3667 oral suspension<br>* GLPG3667 oral suspension<br>|
| Placebo Comparator: Placebo SAD<br>Single doses of placebo | Drug: Placebos<br>* Placebo oral suspension<br>|
| Experimental: GLPG3667 MAD<br>Multiple doses of GLPG3667 at up to 3 dose levels in ascending order, daily for 13 days | Drug: GLPG3667 oral suspension<br>* GLPG3667 oral suspension<br>|
| Placebo Comparator: Placebo MAD<br>Multiple doses of placebo | Drug: Placebos<br>* Placebo oral suspension<br>|
| Experimental: GLPG3667 FE fasted<br>Single dose of GLPG3667 in fasted state | Drug: GLPG3667 oral suspension<br>* GLPG3667 oral suspension<br>|
| Experimental: GLPG3667 FE fed<br>Single dose of GLPG3667 in fed state | Drug: GLPG3667 oral suspension<br>* GLPG3667 oral suspension<br>|
| Experimental: GLPG3667 oral suspension rBA-FE fed<br>Single dose of GLPG3667 oral suspension in fed state | Drug: GLPG3667 oral suspension<br>* GLPG3667 oral suspension<br>|
| Experimental: GLPG3667 capsules rBA-FE fasted<br>Single dose of GLPG3667 capsules in fasted state | Drug: GLPG3667 capsules<br>* GLPG3667 capsules<br>|
| Experimental: GLPG3667 capsules rBA-FE fed<br>Single dose of GLPG3667 capsules in fed state | Drug: GLPG3667 capsules<br>* GLPG3667 capsules<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 GLPG3667, in adult, healthy, male subjects compared with placebo | From screening through study completion, an average of 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration (Cmax) of GLPG3667 (μg/mL) | To evaluate the pharmacokinetics (PK) of single and multiple ascending oral doses of GLPG3667, in adult, healthy, male subjects | Between Day 1 pre-dose and Day 16 | 
| Area under curve (AUC) of GLPG3667 (μg.h/mL) | To evaluate the PK of single and multiple ascending oral doses of GLPG3667, in adult, healthy, male subjects | Between Day 1 pre-dose and Day 16 | 
| Terminal elimination half-life (t1/2) of GLPG3667 (h) | To evaluate the PK of single and multiple ascending oral doses of GLPG3667, in adult, healthy, male subjects | Between Day 1 pre-dose and Day 16 |