Clinical trial NCT02084199: Study to Evaluate GLPG0634 in Subjects With Renal Impairment Compared to Healthy Subjects
Official title: Study to Evaluate the Pharmacokinetics, Safety, Tolerability of 100 mg Multiple Doses of GLPG0634 in Subjects With Renal Impairment Compared to Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
Lead sponsor: Galapagos NV
Sponsor class: INDUSTRY
First posted: 2014-03-11
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This will be an open label study to assess the influence of renal impairment on the pharmacokinetics (PK) of GLPG0634 and its metabolite after once daily oral administrations of 100 mg GLPG0634 for 10 days in subjects with renal impairment and matched healthy controls.

Also, safety and tolerability of once daily oral doses of GLPG0634 for 10 days in subjects with renal impairment and matched healthy controls will be evaluated.

Detailed description: The study will be divided in two parts.

In Part 1, 3 subjects with severe renal impairment or end-stage renal disease (ESRD) not yet requiring dialysis (Group 1) will be recruited first. Thereafter, 3 subjects with normal renal function (Group 2) will be recruited. If a substantial effect on the PK in renal impaired subjects is observed on Day 10, the sponsor may elect to stop Part 1 of the study without enrolling the complete set of subjects and Part 2 will be initiated. In case no substantial effect on the PK is observed, 3 further subjects in both Group 1 and 2 will be recruited and analysed. If a substantial effect on the PK is observed, the study will proceed to Part 2. Part 2 of the study will not be conducted, if in Part 1 no substantial difference in PK is seen.

In Part 2, Group 3 (mild renal impairment) and Group 4 (moderate renal impairment) will be recruited first. After completion of the mild and moderate impairment groups, Group 5 (normal renal function) will be recruited.

Eligibility criteria: Inclusion Criteria:

* Male and female white subjects between 18-79 years of age (inclusive)
* Subjects must have a BMI between 18-34 kg/m², inclusive
* Part 1, Group 1: subject with severe renal impairment or ESRD, not on dialysis : eGFR between 15-29 mL/min/1.73 m2 or \<15 mL/min/1.73m²
* Part 1, Group 2: subject with normal renal function: eGFR ≥90 mL/min/1.73m²
* Part 2, Group 3: subject with mild renal impairment: eGFR between 60-89 mL/min/1.73 m²
* Part 2, Group 4:subject with moderate renal impairment: eGFR between 30-59 mL/min/1.73 m²
* Part 2, Group 5: subject with normal renal function: eGFR ≥90 mL/min/1.73 m²
* Subjects must be judged to be in good health (subjects with normal renal function)/in a stable condition and acceptable for study participation (subjects with renal impairment) based upon the results of a medical history, physical examination, vital signs, 12-lead ECG, and laboratory profile

Exclusion Criteria:

* A subject with a known hypersensitivity to ingredients of the study medication or a significant allergic reaction to any drug
* Subject has previously participated in a GLPG0634 study or has previously received GLPG0634
* Concurrent participation or participation within 8 weeks prior to the initial study drug administration in a drug/device or biologic investigational research study
* A subject with active drug or alcohol abuse within 2 years prior to the initial study drug administration
* A subject who has a current child wish
* Female subject less than 6 months post-partum, post-abortion or post-lactation prior to study drug administration or is pregnant or breastfeeding

Primary outcomes:
measure: Maximum observed plasma concentration (Cmax)
timeFrame: Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)
measure: Area under the plasma drug concentration-time curve over 24 hours (AUC0-24h)
timeFrame: Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)
Secondary outcomes:
measure: Cumulative amount excreted in urine expressed in μg and % of the dose administered (Ae)
timeFrame: Between dosing on Day 1 up to 48 h after dosing on Day 10 (Day 12)
measure: Renal clearance (CLR)
timeFrame: Between dosing on Day 1 up to 48 h after dosing on Day 10 (Day 12)
measure: Plasma concentration observed at 24 h post-dose (C24h)
timeFrame: Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)
measure: Average plasma concentration (Cavg)
timeFrame: Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)
measure: Time of occurrence of Cmax (tmax)
timeFrame: Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)
measure: Area under the plasma drug concentration-time curve from zero to the last sampling time at which concentrations were at or above the limit of quantification (AUC0-z)
timeFrame: Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)
measure: Area under the plasma drug concentration-time curve, extrapolated to infinity (AUC0-∞)
timeFrame: Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)
measure: Apparent terminal half-life (t1/2,λz)
timeFrame: Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)
measure: Metabolite over parent ratio of AUC0-24h (R)
timeFrame: Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)
measure: Accumulation ratio (Rac)
timeFrame: Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)
measure: The number of subjects with adverse events
timeFrame: From screening up to 10 days after last dose (Day 20)
measure: The number of subjects with abnormal laboratory parameters
timeFrame: From screening up to 10 days after last dose (Day 20)
measure: The number of subjects with abnormal vital signs
timeFrame: From screening up to 10 days after last dose (Day 20)
measure: The number of subjects with abnormal electrocardiogram (ECG)
timeFrame: From screening up to 10 days after last dose (Day 20)
measure: The number of subjects with abnormal physical examination
timeFrame: From screening up to 10 days after last dose (Day 20)
Other outcomes:
Locations:
city: Kiel
country: Germany
facility: CRS Clinical Research Services Kiel GmbH
Study officials:
affiliation: Galapagos NV
name: Pille Harrison, MD
role: STUDY_DIRECTOR
References: