PRIMARY OBJECTIVES- To investigate the PK profile of GLPG2451 administered as two doses of a capsule formulation in healthy subjects.- To assess the safety and tolerability of GLPG2451 administered as two doses of a capsule formulation in healthy…
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 GLPG2451 in plasma (including Cmax, AUC)
administered as two doses of a capsule formulation in healthy subjects.
- Determine safety and tolerability of GLPG2451 in healthy subjects, assessed
by the number of subjects with AEs.
Secondary outcome
SECONDARY ENDPOINT
- Determine PK parameters of G1171564 (metabolite of GLPG2451) in plasma.
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. Over 2,000 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 80 to 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 has reduced chloride gating. Thus, patients with the F508del mutation have
very little to no CFTR protein in the apical membrane. CFTR dysfunction results
in viscid secretions that are difficult to clear, affecting most exocrine
glands, notably in 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 a high medical need for adequate therapeutic
approaches targeting the F508del mutation.
Study objective
PRIMARY OBJECTIVES
- To investigate the PK profile of GLPG2451 administered as two doses of a
capsule formulation in healthy subjects.
- To assess the safety and tolerability of GLPG2451 administered as two doses
of a capsule formulation in healthy subjects.
SECONDARY OBJECTIVE
- To investigate the PK profile of G1171564 (metabolite of GLPG2451).
.
Study design
This study is a Phase I, open-label study to investigate the PK of GLPG2451
given as two doses (5 mg and 80 mg) of a capsule formulation
Intervention
1 dose of 5 mg GLPG2451 and after 14 days 1 dose of 80 mg GLPG2451
Study burden and risks
There is no direct benefit to you 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 GPLG2451 are known. Unexpected
side effects might occur. GPLG2451 has been administered to humans before and
has been investigated in laboratories and animal studies. During previous
clinical studies with GLPG2451, the most frequently reported adverse events
were: headache, common cold, shoulder pain, lumboschialgia, loose stools,
decreased appetite, increased energy, sore throat and migraine headache.
Avenue Gaston Roussel 102
Romainville 93230
FR
Avenue Gaston Roussel 102
Romainville 93230
FR
Listed location countries
Age
Inclusion criteria
- Male subject or female subject of non-childbearing potential between 18-50 years of age, inclusive, on the date of signing the informed consent form (ICF).
- Female subjects must 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 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, or test results that are outside the reference ranges need to be considered non-clinically significant in the opinion of the investigator. One retest is allowed if deemed appropriate by the investigator.
- 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) at least 2 weeks prior to the first study drug administration.
- Able and willing to comply with the prohibitions and restrictions and with the contraceptive requirements (male subjects only), as described
in the protocol.
- Able and willing to sign the ICF as approved by the Independent Ethics Committee (IEC), prior to any screening evaluations.;Reference is made to the protocol for a complete overview of the inclusion criteria.
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 prior to screening.
- Presence or having sequelae of gastrointestinal, liver, kidney or other conditions known to interfere with the absorption, distribution,
metabolism, or excretion of drugs.
- Evidence of lens opacity on slit lamp examination or similar system.
- Significant blood loss (including blood donation [>500 mL]), or a transfusion of any blood product within 12 weeks prior to the first study
drug administration.
- Treatment with any drug known to have a well-defined potential for toxicity to a major organ in the last 3 months or 5 times the half-life of
the drug (whichever is longer) prior to the first study 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 the first study drug administration.;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 | EUCTR201700087412-NL |
| CCMO | NL61239.056.17 |