A Study to Assess Safety, Tolerability and Pharmacokinetics of GLPG3067 in Healthy Subjects.

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.

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: GLPG3067 single dose; Drug: Placebo single dose; Drug: GLPG3067 oral suspension; Drug: GLPG3067 oral tablet; Drug: GLPG3067 multiple dose; Drug: Placebo multiple dose; Drug: GLPG3067/GLPG2222 multiple dose; Drug: GLPG3067/GLPG2222 Placebo multiple dose; Drug: GLPG3067/GLPG2222/GLPG2737 multiple dose; Drug: GLPG3067/GLPG2222/GLPG2737 Placebo multiple dose

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium
    • SGS LSS Clinical Pharmacology Unit Antwerp

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GLPG3067 single dose; Single dose of GLPG3067 oral suspension at up to 6 dose levels in ascending order.	Drug: GLPG3067 single dose; GLPG3067 oral suspension, single ascending doses, daily
Placebo Comparator: Placebo single dose; Single dose of Placebo oral suspension.	Drug: Placebo single dose; Placebo, oral suspension, daily
Experimental: GLPG3067 oral suspension fed 1; Single dose 1 of GLPG3067 oral suspension after a standardized breakfast.	Drug: GLPG3067 oral suspension; GLPG3067 oral suspension, single dose, daily
Experimental: GLPG3067 oral tablet fed 1; Single dose 1 of GLPG3067 oral tablet after a standardized breakfast.	Drug: GLPG3067 oral tablet; GLPG3067 oral tablet, single dose, daily
Experimental: GLPG3067 oral tablet fasted 1; Single dose 1 of GLPG3067 oral tablet after an overnight fast.	Drug: GLPG3067 oral tablet; GLPG3067 oral tablet, single dose, daily
Experimental: GLPG3067 oral tablet fed 2; Single dose 2 of GLPG3067 oral tablet after a standardized breakfast.	Drug: GLPG3067 oral tablet; GLPG3067 oral tablet, single dose, daily
Experimental: GLPG3067 oral tablet fed 2 high-fat high-calorie; Single dose 2 of GLPG3067 oral tablet after a high-fat high-calorie breakfast	Drug: GLPG3067 oral tablet; GLPG3067 oral tablet, single dose, daily
Experimental: GLPG3067 multiple dose; Multiple doses of GLPG3067 oral suspension at up to 5 dose levels in ascending order.	Drug: GLPG3067 multiple dose; GLPG3067 oral suspension, multiple ascending doses, daily for 14 days
Placebo Comparator: Placebo multiple dose; Multiple doses of Placebo oral suspension.	Drug: Placebo multiple dose; Placebo, oral suspension, daily for 14 days
Experimental: GLPG3067/GLPG2222 multiple dose; Multiple doses of GLPG3067 oral suspension combined with GLPG2222 oral tablet up to 2 dose levels in ascending order.	Drug: GLPG3067/GLPG2222 multiple dose; GLPG3067 oral suspension and GLPG2222 oral tablet, multiple doses, daily for 14 days
Placebo Comparator: GLPG3067/GLPG2222 Placebo multiple dose; Multiple doses of GLPG3067 matching placebo oral suspension combined with GLPG2222 matching placebo oral tablet.	Drug: GLPG3067/GLPG2222 Placebo multiple dose; GLPG3067 matching placebo oral suspension and GLPG2222 matching placebo oral tablet, multiple doses, daily for 14 days
Experimental: GLPG3067/GLPG2222/GLPG2737 multiple dose; Multiple doses of GLPG3067 oral tablet combined with GLPG2222 oral tablet and GLPG2737 oral capsule at up to 2 dose levels in ascending order.	Drug: GLPG3067/GLPG2222/GLPG2737 multiple dose; GLPG3067 oral tablet, GLPG2222 oral tablet and GLPG2737 oral capsule, multiple doses, daily for 14 days
Placebo Comparator: GLPG3067/GLPG2222/GLPG2737 Placebo multiple dose; Multiple doses of GLPG3067 matching placebo oral tablet combined with GLPG2222 matching placebo oral tablet and GLPG2737 matching placebo oral capsule.	Drug: GLPG3067/GLPG2222/GLPG2737 Placebo multiple dose; GLPG3067 matching placebo oral tablet, GLPG2222 matching placebo oral tablet and GLPG2737 matching placebo oral capsule, multiple doses, daily for 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change versus placebo in the proportion of subjects with adverse events	To assess safety and tolerability of single ascending doses, multiple ascending doses of GLPG3067 alone, or in combination with GLPG2222, or in combination with GLPG2222 and GLPG2737 versus placebo in healthy subjects	Between screening and 14 days after the last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed plasma concentration of GLPG3067 (Cmax) given alone or in combination with GLPG2222 or in combination with GLPG2222 and GLPG2737	To characterize pharmacokinetics of GLPG3067 after a single oral dose and of GLPG3067, GLPG2222, and GLPG2737 after multiple oral doses in healthy subjects	Between Day 1 predose and 10 days after the last dose
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	To characterize pharmacokinetics of GLPG3067 after a single oral dose and of GLPG3067, GLPG2222, and GLPG2737 after multiple oral doses in healthy subjects	Between Day 1 predose and 10 days after the last dose
Ratio of 4-beta-hydroxycholesterol/cholesterol in plasma after multiple oral doses in healthy subjects	To assess the potential for CYP3A4 interaction with GLPG3067, GLPG3067 and GLPG2222, or GLPG3067 and GLPG2222 and GLPG2737	Day 1 predose and Day 14
Maximum observed plasma concentration of GLPG3067 (Cmax) given alone in fed state	To assess the relative bioavailability of GLPG3067 when given as a single dose of oral suspension or an oral tablet both administered in fed state	Between Day 1 predose and 10 days after the last dose
Concentration in plasma observed at 24 hours post dose (C24h) of GLPG3067 given alone in fed state	To assess the relative bioavailability of GLPG3067 when given as a single dose of oral suspension or an oral tablet both administered in fed state	Between Day 1 predose and 10 days after the last dose
Area under the plasma concentration-time curve of GLPG3067 (AUC0-t) given alone in fed state	To assess the relative bioavailability of GLPG3067 when given as a single dose of oral suspension or an oral tablet both administered in fed state	Between Day 1 predose and 10 days after the last dose
Maximum observed plasma concentration of GLPG3067 (Cmax) given alone in fasted state	To assess the effect of food on the pharmacokinetics of GLPG3067 when given under fasted versus fed conditions	Between Day 1 predose and 10 days after the last dose
Concentration in plasma observed at 24 hours post dose (C24h) of GLPG3067 given alone in fasted state	To assess the effect of food on the pharmacokinetics of GLPG3067 when given under fasted versus fed conditions	Between Day 1 predose and 10 days after the last dose
Area under the plasma concentration-time curve of GLPG3067 (AUC0-t) given alone in fasted state	To assess the effect of food on the pharmacokinetics of GLPG3067 when given under fasted versus fed conditions	Between Day 1 predose and 10 days after the last dose

Collaborators and Investigators

• Sponsor: Galapagos NV

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2017
• Primary Completion (Actual): February 20, 2018
• Study Completion (Actual): February 20, 2018

Study Registration Dates

• First Submitted: April 21, 2017
• First Submitted That Met QC Criteria: April 21, 2017
• First Posted (Actual): April 25, 2017

Study Record Updates

• Last Update Posted (Actual): April 10, 2018
• Last Update Submitted That Met QC Criteria: April 9, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: GLPG3067-CL-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No