Primary:To evaluate the effect of GLPG3970 on the pharmacokinetics (PK) of methotrexate (MTX) and its active metabolite 7-hydroxymethotrexate (7-OH MTX) in healthy subjectsTo evaluate the effect of GLPG3970 on the PK of sulfasalazine and its active…
Source
Brief title
Condition
- Other condition
Synonym
Health condition
chronic inflammatory diseases
Research involving
Sponsors and support
Intervention
No registrations found.
Outcome measures
Primary outcome
MTX and 7-OH MTX PK parameters: maximum observed concentration (Cmax) and area
under the plasma concentration-time curve from time zero to
infinity (AUC0-*)
Sulfasalazine and sulfapyridine PK parameters:
Cmax and AUC0-*
Sulfapyridine to sulfasalazine AUC ratio
Secondary outcome
Safety and tolerability, assessed by the incidence and severity of treatment
emergent adverse events (TEAEs)
Safety and tolerability, assessed by the incidence and severity of TEAEs
GLPG3970 PK parameters such as trough concentrations (Ctrough), Cmax, time of
occurrence of Cmax (tmax), and AUC0-t
Background summary
GLPG3970 is a new compound that may eventually be used for the treatment of
chronic inflammatory diseases, such as rheumatoid arthritis and inflammatory
bowel disease. GLPG3970 is an inhibitor (suppressor) of a certain substance
called a kinase, which regulates cytokines. Cytokines are signaling substances
that regulate the immune response and these kinases play an important role in
the production and balance of pro-inflammatory and anti-inflammatory cytokines.
GLPG3970 is expected to shift the balance of these cytokines so the immune
system starts working better, and the inflammation decreases.
Methotrexate (MTX) and sulfasalazine are common background therapies in RA and
IBD and consequently they will be used in future clinical studies with
GLPG3970. This clinical study will therefore assess the potential for a
drug-drug interaction (DDI) following coadministration of GLPG3970 with these
intended concomitant medications.
Study objective
Primary:
To evaluate the effect of GLPG3970 on the pharmacokinetics (PK) of methotrexate
(MTX) and its active metabolite 7-hydroxymethotrexate (7-OH MTX) in healthy
subjects
To evaluate the effect of GLPG3970 on the PK of sulfasalazine and its active
metabolite sulfapyridine in healthy subjects
Secondary:
To evaluate the safety and tolerability of the coadministration of GLPG3970
with MTX in healthy subjects
To evaluate the safety and tolerability of the coadministration of GLPG3970
with sulfasalazine in healthy subjects
To evaluate the PK of GLPG3970 in presence of MTX or sulfasalazine in healthy
subjects
Study design
This is a non-randomized, fixed sequence, open-label, drug-drug interaction
(DDI) study designed to assess
the impact of concomitant administration of GLPG3970, a potential in vivo
breast cancer resistance protein
(BCRP) inhibitor, on the PK of MTX and sulfasalazine, both BCRP substrates.
The study will consist of 2 separate assessments performed in 2 parallel groups.
Group 1 will receive a single oral dose of MTX alone (Period 1), followed by a
single oral dose of MTX in
combination with repeated dosing with GLPG3970 (Period 2).
Group 2 will receive a single dose of sulfasalazine alone (Period 1), a single
dose of sulfasalazine in
combination with a single dose of GLPG3970 (Period 2), followed by a single
dose of sulfasalazine given
2 hours prior to a single dose of GLPG3970 (Period 3).
The study will consist of a screening period of up to 6 weeks, an open-label
study period of 11 days for
Group 1 and 14 days for Group 2, and a follow-up (FU) period of 2 weeks
following the last investigational
medicinal product (IMP) administration.
Subjects in both groups will be confined to the site during the entire
treatment and PK blood collection
periods.
Intervention
Group 1:
Day/ Treatment/ Timing
1) 7.5 mg methotrexate as 3 oral tablets of 2.5 mg
5) 350 mg GLPG3970 as oral solution 7.5 mg methotrexate as 3 oral tablets of
2.5 mg
A maximum of 1 minute between GLPG3970 and methotrexate administration
6-8) 350 mg GLPG3970 as oral solution
Group 2:
Day/ Treatment/ Timing
1) 1000 mg sulfasalazine as 2 oral tablets of 500 mg
5) 350 mg GLPG3970 as oral solution 1000 mg sulfasalazine as 2 oral tablets of
500 mg
A maximum of 1 minute between GLPG3970 and sulfasalazine administration
9) 1000 mg sulfasalazine as 2 oral tablets of 500 mg 350 mg GLPG3970 as oral
solution
Sulfasalazine will be administered 2 hours before GLPG3970
Study burden and risks
GLPG3970
The study compound may cause side effects.
A clinical study in which GLPG3970 is administered for the first time in humans
is currently ongoing. Overall, no mortalities or other SAEs have been reported
to date and an ongoing-blinded review of adverse events (AEs), vital signs,
laboratory safety tests, ECG morphology and ECG time intervals indicate that
single doses of GLPG3970 up to 500 mg and 14 days repeated once daily doses of
GLPG3970 up to 400 mg have been well-tolerated.
The study compound may also have side effects that are still unknown. In
addition to unknown side effect, there is a (small) chance that an allergic
reaction will occur. This can be caused by the study compound or the
excipients.
If during the study more information becomes available regarding side effects
that may be related to the study compound, the responsible doctor will inform
the volunteer about this.
Methotrexate
Methotrexate is used to treat psoriasis and other inflammatory diseases.
The very common side effects are (>10%): inflammation and ulceration of the
mucosa of the mouth and throat (especially during the first 24-48 hours after
administration), dyspepsia (indigestion), loss of appetite, abdominal pain,
nausea, vomiting, increase in liver enzymes.
The common side effects are (1-10%): diarrhea (especially during the first
24-48 hours after administration), rash, erythema (redness of the skin),
pruritus (itch), headache, fatigue, drowsiness, pneumonia, interstitial
alveolitis/pneumonitis (inflammation of the lung), leukopenia (decrease in
white blood cell count), anemia (decrease in red blood cell count),
thrombocytopenia (decrease in blood platelet count).
These side effects are seen in patients who took methotrexate for a longer
period of time.
Sulfasalazine
Sulfasalazine can be used for the treatment of Crohn disease (chronic
inflammation of the digestive tract, such as the intestines).
The very common side effects are (> 10%): stomach complaints, nausea.
The common side effects are (1-10%): leukopenia (decrease in white blood cell
count), decreased appetite, dizziness, headache, taste disturbances, tinnitus,
cough, abdominal pain, diarrhea, vomiting, pruritus (itch), purpura (blood
spots or skin hemorrhages), arthralgia (joint pain), proteinuria (increase of
protein in urine), fever.
These side effects are seen in patients who took sulfasalazine for a longer
period of time.
Generaal De Wittelaan L11 A3
Mechelen 2800
BE
Generaal De Wittelaan L11 A3
Mechelen 2800
BE
Listed location countries
Age
Inclusion criteria
1. Male or female Caucasian between 18-55 years of age (extremes included), on
the date of signing the informed consent form (ICF).
2. Females should be of non-childbearing potential defined as permanently
surgically sterile (bilateral oophorectomy, i.e. surgical removal of ovaries,
bilateral salpingectomy or hysterectomy, i.e. surgical removal of uterus), or
with no menses for 12 or more months without an alternative medical cause AND a
follicle-stimulating hormone (FSH) level >35 IU/L. These subjects must also
have a negative pregnancy test. For surgical sterilization, documented
confirmation will be requested.
3. A body mass index (BMI) between 18-30 kg/m2, inclusive.
4. A BCRP c421C/C genotype.
5. Judged to be in good health by the investigator based upon the results of a
medical history, physical examination, vital signs, 12-lead electrocardiogram
(ECG), and fasting clinical laboratory safety tests, available at screening and
prior to the first non investigational medicinal product (NIMP) administration.
Bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT)
must be no greater than 1.5x upper limit of normal range (ULN). Other clinical
laboratory safety test results must be within the reference ranges or test
results that are outside the reference ranges need to be considered not
clinically significant in the opinion of the investigator.
Exclusion criteria
1. Known hypersensitivity to the IMP (GLPG3970), or NIMPs (MTX and
sulfasalazine), or sulfa drugs, or to their ingredients, or history of a
significant allergic reaction to IMP or NIMPs ingredients as determined by the
investigator.
2. Positive serology for hepatitis B virus surface antigen (HBsAg) or hepatitis
C virus (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
NIMP.
3. History of or a current immunosuppressive condition (e.g. human
immunodeficiency virus [HIV]
infection).
4. Having any illness, judged by the investigator as clinically significant, in
the 3 months prior to first
dosing of the NIMP.
5. Presence or sequelae of gastrointestinal, liver, kidney (creatinine
clearance <=80 mL/min using the
Cockcroft-Gault formula: if calculated result is <=80 mL/min, a 24-hours urine
collection can be done) or other conditions known to interfere with the
absorption, distribution, metabolism, or excretion of drugs.
6. Subjects with a N-acetyltransferase (NAT) 2 slow acetylator genotype (only
applicable to Group 2
receiving sulfasalazine).
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 | EUCTR2020-000391-37-NL |
CCMO | NL73255.056.20 |