Clinical trial NCT04653467: A Study to Evaluate How Well Single and Multiple Doses of GLPG4399 Are Tolerated in Healthy, Adult Subjects
Official title: 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 GLPG4399 in Adult, Healthy, Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Galapagos NV
Sponsor class: INDUSTRY
First posted: 2020-12-04
Enrollment: 88
Sex: MALE
Minimum age (years): 18
Maximum age (years): 54
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Part 1: a randomized, double-blind, single ascending dose (SAD), Part 2: a randomized, double-blind, multiple ascending dose (MAD) escalation and Part 3 and 4: an open-label, randomized, crossover rBA and food-effect (FE) part.
Primary purpose: BASIC_SCIENCE

Brief summary: The main purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single (part 1) and multiple ascending (part 2) oral doses of GLPG4399, in adult, healthy, male subjects. In addition, the effect of food and the relative bioavailability (rBA) of GLPG4399, will be evaluated (part 3 and 4).


Eligibility criteria: 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 ECG, and fasting clinical laboratory safety tests, available at screening and prior to randomization. Total 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.
* 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.
* Able and willing to comply with the clinical study protocol (CSP) requirements and to sign and date the ICF as approved by the Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to any screening evaluations.

Exclusion Criteria:

* Subject has a history of any drug allergies.
* 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.
* Subject testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as detected by real-time polymerase chain reaction (RT-PCR) or subjects who have been in contact with SARS-CoV-2 infected individuals in the 2 weeks prior to first dosing of IP. Subjects presenting any signs or symptoms of SARS-CoV-2 infection as detected at screening and/or baseline following careful physical examination (e.g. cough, fever, headaches, fatigue, dyspnea, myalgia, anosmia, dysgeusia, anorexia, sore throat, etc.) will also be excluded. In addition, any other locally applicable standard diagnostic criteria may also apply to diagnose SARS-CoV-2 infection.
* 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 modification of diet in renal disease (MDRD) formula) or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
* History of malignancy within the past 5 years prior to screening with the exception of excised and curatively treated non-metastatic basal cell carcinoma or squamous cell carcinoma of the skin which is considered cured with minimal risk of recurrence.
* Vital sign abnormalities (systolic blood pressure \<90 or \>140 mmHg, diastolic blood pressure \<60 or \>90 mmHg, or heart rate \<60 or \>100 bpm) at screening.
* History or presence of clinically significant abnormalities detected on 12-lead ECG of either rhythm or conduction e.g. known long QT syndrome or a QT interval corrected for heart rate using Fridericia's formula: QTcF = QT/RR1/3 (QTcF) \>450 ms detected on the 12-lead ECG. A first-degree atrioventricular block will not be considered as a significant abnormality.
* Personal or family history of long QT syndrome or unexplained sudden cardiac death in a first-degree relative.
* Male subjects with female partners of child bearing potential not willing to comply with the contraceptive methods
* Significant blood loss (including blood donation \[\>450 mL\]), or transfusion of any blood product within 12 weeks prior to (first) dosing.
* Treatment with any drug known to have a potential for major organ toxicity in the last 3 months before first dosing of the IP.
* Treatment with any medication (including over-the-counter (OTC) and/or prescription medication, dietary supplements, nutraceuticals, vitamins and/or herbal supplements) 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 of IP.
* Active drug abuse or alcohol abuse (alcohol abuse defined as regular weekly intake of more than 14 units1) within 2 years prior to first IP administration.
* Active smoker and/or has used e-cigarettes, nicotine, or nicotine-containing products within the past 6 months before the first IP administration.
* Regular consumption of a large quantity of caffeinated coffee, tea (\>6 cups per day) or equivalent.
* Concurrent participation or participation in a drug, drug/device or biologic investigational research study within 12 weeks or 5 half-lives of the IP, whichever is longer, prior to first dosing.
* Investigator or other study staff or relative thereof who is directly involved in the conduct of the study.
* Any condition or circumstances that in the opinion of the investigator may make a subject unlikely or unable to complete the study or comply with study procedures and requirements.

Primary outcomes:
measure: Frequency and severity of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (SAEs), and TEAEs leading to treatment discontinuations.
timeFrame: From screening through study completion, an average of 6 months
Secondary outcomes:
measure: Maximum observed plasma concentration (Cmax) of GLPG4399
timeFrame: Between Day 1 pre-dose and Day 33
measure: Area under curve (AUC) of GLPG4399
timeFrame: Between Day 1 pre-dose and Day 33
measure: Terminal elimination half-life (t1/2) of GLPG4399
timeFrame: Between Day 1 pre-dose and Day 33
Other outcomes:
Locations:
city: Mont-Royal
country: Canada
facility: Altasciences Montreal
Study officials:
affiliation: Galapagos NV
name: Magdalena Petkova, MD
role: STUDY_DIRECTOR
References: