- To assess the relative bioavailability of GLPG2737 administered as a single capsule compared to a single oral suspension in the fed state.- To assess the safety and tolerability in healthy subjects of GLPG2737 administered as a capsule and as an…
ID
Source
Brief title
Condition
- Other condition
- Congenital and hereditary disorders NEC
Synonym
Health condition
Cystic fibrosis
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Determine PK parameters of GLPG2737 in plasma after administration of a
single dose of a suspension and of a capsule formulation in healthy subjects.
- Determine safety and tolerability of GLPG2737 in healthy male subjects, as
assessed by the number of subjects with adverse events (AEs).
Secondary outcome
Not applicable
Background summary
Cystic fibrosis (CF) is caused by mutations in the gene encoding for the cystic
fibrosis transmembrane conductance regulator (CFTR) protein, a cyclic adenosine
monophosphate (cAMP)-regulated anion channel expressed primarily at the apical
plasma membrane of secretory epithelia. Nearly 2000 mutations in the CFTR gene
(CFTR) have been identified, which are grouped into six classes (class I-VI).
The F508del mutation is by far the most common CFTR mutation globally,
especially in the Caucasian population. Approximately 90% of CF patients in the
United States and Europe have at least one copy of this mutation on one allele,
with almost half of them being F508del homozygous (i.e. the mutation is present
on both alleles). The F508del mutation impairs CFTR folding, trafficking
towards the plasma membrane, has reduced plasma membrane stability, and reduced
chloride gating. Thus, patients with the F508del mutation have very little to
no CFTR protein at the apical membrane. The absence of CFTR function results in
viscid secretions that are difficult to clear, affecting most exocrine glands,
notably the pancreas, intestine, liver, and bile duct. However, most morbidity
and mortality results from dehydration of the airway surface liquid and
impaired airway mucociliary clearance, which leads to cycles of bacterial
infection, chronic inflammation, bronchiectasis and progressive decline in
pulmonary function. There is currently an unmet medical need for adequate
therapeutic approaches to treat CF patients with the F508del mutation.
Study objective
- To assess the relative bioavailability of GLPG2737 administered as a single
capsule compared to a single oral suspension in the fed state.
- To assess the safety and tolerability in healthy subjects of GLPG2737
administered as a capsule and as an oral suspension in healthy male subjects.
Study design
This is a Phase I, open-label, randomized, single-dose, two-way crossover study
to explore the relative bioavailability of GLPG2737 given as a capsule
formulation compared to an oral suspension in the fed state.
Intervention
a single dose of GLPG2737 on two occasions
Study burden and risks
There is no direct benefit for the subjects from taking part in the study. The
results of the study will provide valuable information for future
research. Not all side effects of new compounds, such as GPLG2737 are known.
Unexpected side effects might occur.
Generaal De Wittelaan L11 A3
Mechelen 2800
BE
Generaal De Wittelaan L11 A3
Mechelen 2800
BE
Listed location countries
Age
Inclusion criteria
- Male between 18-50 years of age, inclusive, on the date of signing the Informed Consent Form (ICF).
- A body mass index (BMI) 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 ECG, and clinical safety laboratory tests prior to the initial study drug administration. Clinical safety laboratory test results must be within the laboratory reference ranges for males or test results that are outside the reference ranges for males need to be considered non clinically significant in the opinion of the investigator. One retest is allowed if deemed appropriate by the investigator without asking permission from the sponsor.
- Discontinuation of all medications (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 maximum of 10 g/2 weeks) least 2 weeks prior to the first study drug administration.;Reference is made to the protocol for a complete overview of the inclusion criteria.
Exclusion criteria
* History of or a current immunosuppressive condition (e.g., human immunodeficiency virus [HIV] infection type 1 and 2).
* Clinically significant illness in the 3 months before screening.
* Presence or having sequelae of gastrointestinal, liver, kidney (creatinine clearance [CLCR] * 80 mL/min using the Cockcroft-Gault formula: if calculated result * 80 mL/min, a 24 hour urine collection to determine actual value can be done) or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
* Treatment with any drug known to have a well-defined potential for toxicity to a major organ within the last 3 months or 5-half-lives of the drug (whichever is longer) before the initial drug administration.
* 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 screening.;Reference is made to the protocol for a complete overview of the exclusion criteria.
Design
Recruitment
Medical products/devices used
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 | EUCTR2016-004984-38-NL |
| CCMO | NL61566.056.17 |