To evaluate the safety and tolerability of single and multiple ascending oral doses of GLPG3312, in adult, healthy subjects, when given as IR or as MR formulation compared with placebo.To evaluate the PK of single and multiple ascending oral doses…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Ontstekingsziekten zoals IBD
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Frequency and severity of treatment-emergent adverse events (TEAEs),
treatment-emergent SAEs, and TEAEs leading to treatment discontinuations, in
adult, healthy subjects.
Secondary outcome
Plasma, urine, and stool (Part 4 only) PK parameters of GLPG3312 in adult,
healthy subjects: maximum observed plasma concentration (Cmax), area under the
plasma concentration-time curve (AUC), Aefeces, AEurine, t1/2.
Ratio in extent and exposure following dosing of GLPG3312 as a MR formulation,
under fed conditions (high-fat high-calorie) versus fasted conditions, in
adult, healthy subjects.
Background summary
GLPG3312 is a first-in-class drug in clinical development for the treatment of
inflammatory bowel diseases. In experimental IBD animal models a dose-dependent
improvement has already been demonstrated in disease activity and symptoms
related to inflammatory bowel. This research aims at an initial evaluation of
the safety, pharmacokinetics and pharmacodynamics of GLPG3312 in humans.
Study objective
To evaluate the safety and tolerability of single and multiple ascending oral
doses of GLPG3312, in adult, healthy subjects, when given as IR or as MR
formulation compared with placebo.
To evaluate the PK of single and multiple ascending oral doses of GLPG3312, in
adult, healthy subjects, when given as IR or as MR formulation.
To explore the food-effect (FE) on the PK of a single oral dose of GLPG3312, in
adult, healthy subjects, when given as MR formulation
Study design
Part A: The actual study will consist of 1 period during which the subject will
stay in the research center for 6 days (5 nights).
Part B: The actual study will consist of 1 period during which the subject will
stay in the research center for 6 days (5 nights) / 7 days (7 nights for group
K and any optional cohorts)
Part C: The actual study will consist of 2 periods during which the subject
will stay in the research center for 8 days (7 nights).
Part D: The actual study will consist of 1 period during which the subject will
stay in the research center for 22 days (21 nights).
GLPG3312 or placebo or placebo will be given as oral tablets with 240
milliliters (mL) of (tap) water.
Part 1: For safety reasons, initially 2 volunteers will receive the study
compound in each group. One volunteer will receive GLPG3312, and 1 will receive
placebo. After administration, the safety and tolerability of the study
compound in these 2 volunteers will be closely monitored. If there are no
concerns about the safety and tolerability 24 hours after administration, then
the remaining 6 volunteers (5 will receive GLPG3312 and 1 will receive placebo)
in each group will receive the study compound.The study medication will be
administered double-blind.
Part 2: Whether the subject will receive GLPG3312 or placebo will be determined
by chance. Per group, 6 volunteers will receive GLPG3312 and 2 volunteers will
receive placebo.
Part 3: The subject will receive the study compound once with a breakfast and
once without breakfast. The order in which this will occur will be determined
by chance. In one period the subject will receive a high-fat breakfast with a
standard composition, which must be started exactly on time and must be
finished within 20 minutes. The entire breakfast must be consumed. In the other
period the subject will receive the study compound in a fasted condition. There
will be a washout period of at least 7 days between administrations of the
study compound.
Part 4: The subject will receive GLPG3312 or placebo via a dosing cup
(containing mini-tablets) or as a capsule (also containing mini-tablets) by
mouth. It will be given with 240 milliliters (ml) of (tap) water. This will
depend on the on the tolerability and safety data that are collected during the
study.
Intervention
GLPG3312 or placebo or placebo will be given as oral tablets with 240
milliliters of (tap) water.
See section 'Study Design' for more details about the intervention.
Study burden and risks
The study compound may cause side effects.
GLPG3312 was administered to humans for the first time in part 1 of this study.
After prolonged daily administration of GLPG3312 in rats and dogs, adverse
reactions were observed during 6 weeks, which were not observed after 7 and 14
days of administration of a single dose.
Drawing blood and/or insertion of the indwelling cannula may be painful or
cause some bruising.
In total, we will take a maximum of 240milliliters (mL) of blood from the
subject. This amount does not cause any problems in adults.
To make a heart tracing, electrodes (small, plastic patches) will be pasted at
specific locations on the subjects arms, chest and legs. Prolonged use of these
electrodes can cause skin irritation (rash and itching).
Generaal De Wittelaan L11 A3
Mechelen 2800
BE
Generaal De Wittelaan L11 A3
Mechelen 2800
BE
Listed location countries
Age
Inclusion criteria
- Male or female between 18 to 55 years of age (extremes included), on the date
of signing the ICF. Females should be of non-childbearing potential as defined
in the protocol.
- A body mass index (BMI) between 18 to 30 kg/m2, inclusive.
- Subject must be able and willing to comply with restrictions on prior
medication.
- Male subjects with female partners of childbearing potential must be willing
to comply with contraceptive methods.
Exclusion criteria
- Positive serology for HBsAg, or 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.
- History of, or a current immunosuppressive condition (e.g. HIV infection).
- Having any illness judged by the investigator as clinically significant, in
the 3 months prior to first dosing of the IMP.
- Any history, or current sign or symptom of a cardiovascular, renal, or
metabolic bone disease or disease of bone remodeling, or any history of
endocrine disease, including an abnormal laboratory result for prespecified
clinical laboratory safety parameters related to these conditions.
- History of malignancy within the past 5 years prior to screening with the
exception of excised and curatively treated nonmetastatic cell carcinoma of the
skin or carcinoma in situ of cervix which is considered cured with minimal risk
of recurrence.
- Significant blood loss (including blood donation >450 mL), or transfusion of
any blood product within 12 weeks prior to screening.
- Treatment with any medication (including over-the-counter and/or prescription
medication, dietary supplements, nutraceuticals, vitamins and/or herbal
supplements) except occasional paracetamol (maximum dose of 2 g/day and a
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 the IMP.
- Active drug abuse or alcohol abuse (alcohol abuse defined as regular weekly
intake of more than 14 units) within 2 years prior to first IMP administration.
- Active smoker and/or has used nicotine or nicotine-containing products within
the past 6 months before the first IMP 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 IMP,
whichever is longer, prior to first dosing of the IMP.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-001955-11-NL |
| ClinicalTrials.gov | NCT03800472 |
| CCMO | NL68190.056.18 |