Clinical trial NCT03128606: A Study to Assess Safety, Tolerability and Pharmacokinetics of GLPG3067 in Healthy Subjects.
Official title: Assessment of Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Oral Doses of GLPG3067, the Combination of GLPG3067 and GLPG2222, and the Combination of GLPG3067, GLPG2222 and GLPG2737 in Healthy Female Subjects, Including a Relative Bioavailability and Food Effect Part for Single Dose of GLPG3067.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Galapagos NV
Sponsor class: INDUSTRY
First posted: 2017-04-25
Enrollment: 81
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

Brief summary: The study is a First-in-Human, Phase I, randomized, double-blind, placebo-controlled, single center study, evaluating single and multiple ascending oral doses of GLPG3067 and the combination of GLPG3067 and GLPG2222 and the combination of GLPG3067,GLPG2222 and GLPG2737 given for 14 days in healthy women of non-childbearing potential.

The purpose of the study is to evaluate the safety and tolerability of single ascending oral doses and multiple ascending oral doses of GLPG3067 given to healthy women of non-childbearing potential compared to placebo, as well as of multiple oral doses of the combination of GLPG3067/GLPG2222 compared to matching placebo for each compound and multiple oral doses of the combination of GLPG3067/GLPG2222/GLPG2737 compared to matching placebo for each compound.


Eligibility criteria: Inclusion Criteria:

* Female subject between 18-70 years of age, inclusive, on the date of signing the informed consent form (ICF).
* Be of non-childbearing potential defined as surgically sterile (hysterectomy, bilateral salpingectomy and bilateral oophorectomy), or post-menopausal (at least 12 consecutive months without menstruation, without an alternative medical cause \[including hormone replacement therapy\]).
* Have a body mass index between 18-30 kg/m2, inclusive.
* Judged by the investigator to be in good health based upon the results of a medical history, physical examination, vital signs, 12-lead triplicate electrocardiogram (ECG), and clinical safety laboratory tests prior to the initial study drug administration.
* Discontinuation of all medications (including over-the-counter and/or prescription medication, dietary supplements, nutraceuticals, vitamins and/or herbal supplements, and hormonal replacement therapy for postmenopausal subjects) except occasional paracetamol (maximum dose of 2 g/day and maximum of 10 g/2 weeks) at least 2 weeks prior to the first study drug administration.

Exclusion Criteria:

* Known hypersensitivity to study drug ingredients or a significant allergic reaction to any drug as determined by the investigator, such as anaphylaxis requiring hospitalization.
* Clinically significant symptoms or illness in the 3 months before screening.
* Presence or having sequelae of gastrointestinal, liver, kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
* Any laboratory result considered by the investigator as clinically significant prior to study drug administration.
* Creatinine clearance ≤80 mL/min using the Cockcroft-Gault formula for subjects aged ≤50 years, or creatinine clearance ≤70 mL/min using the Cockcroft-Gault formula for subjects aged \>50 years. A 24-hour urine collection to determine the actual value may be performed to confirm creatinine clearance if required.
* Clinically significant abnormalities of vital signs at screening.
* Clinically relevant abnormalities detected on ECG regarding either rhythm or conduction (e.g. QT interval corrected for heart rate using Fridericia's formula \[QTcF\] \>470 ms) or a known long QT syndrome. A first degree heart block or sinus arrhythmia will not be considered as a significant abnormality.
* Participation in a drug, drug and device delivery system or combination, or biologic investigational research study within 8 weeks or 5 times the half-life of the investigational drug, if the half-life is known (whichever is longer) prior to initial study drug administration. Subjects who have been dosed previously with GLPG3067 in a clinical trial are allowed to participate Part 4 of this study as long as they completed their last follow-up visit or a washout period of 5 times the half-life of GLPG3067 (whichever is longer) after the last study drug administration is respected.

Primary outcomes:
measure: Change versus placebo in the proportion of subjects with adverse events
timeFrame: Between screening and 14 days after the last dose
Secondary outcomes:
measure: Maximum observed plasma concentration of GLPG3067 (Cmax) given alone or in combination with GLPG2222 or in combination with GLPG2222 and GLPG2737
timeFrame: Between Day 1 predose and 10 days after the last dose
measure: Area under the plasma concentration-time curve of GLPG3067 (AUC0-t) given alone or in combination with GLPG2222 or in combination with GLPG2222 and GLPG2737
timeFrame: Between Day 1 predose and 10 days after the last dose
measure: Ratio of 4-beta-hydroxycholesterol/cholesterol in plasma after multiple oral doses in healthy subjects
timeFrame: Day 1 predose and Day 14
measure: Maximum observed plasma concentration of GLPG3067 (Cmax) given alone in fed state
timeFrame: Between Day 1 predose and 10 days after the last dose
measure: Concentration in plasma observed at 24 hours post dose (C24h) of GLPG3067 given alone in fed state
timeFrame: Between Day 1 predose and 10 days after the last dose
measure: Area under the plasma concentration-time curve of GLPG3067 (AUC0-t) given alone in fed state
timeFrame: Between Day 1 predose and 10 days after the last dose
measure: Maximum observed plasma concentration of GLPG3067 (Cmax) given alone in fasted state
timeFrame: Between Day 1 predose and 10 days after the last dose
measure: Concentration in plasma observed at 24 hours post dose (C24h) of GLPG3067 given alone in fasted state
timeFrame: Between Day 1 predose and 10 days after the last dose
measure: Area under the plasma concentration-time curve of GLPG3067 (AUC0-t) given alone in fasted state
timeFrame: Between Day 1 predose and 10 days after the last dose
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: SGS LSS Clinical Pharmacology Unit Antwerp
Study officials:
affiliation: Galapagos NV
name: Magdalena Petkova, MD
role: STUDY_DIRECTOR
References: