Study to Evaluate GLPG0634 in Subjects With Renal Impairment Compared to Healthy Subjects

Study to Evaluate the Pharmacokinetics, Safety, Tolerability of 100 mg Multiple Doses of GLPG0634 in Subjects With Renal Impairment Compared to Healthy Subjects

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.

Study Overview

• Status: Completed
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: GLPG0634

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Kiel, Germany
    • CRS Clinical Research Services Kiel GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 - Severe renal impairment; Part 1 - Group 1: subjects with severe renal impairment or end-stage renal disease (ESRD), not on dialysis: Estimated glomerular filtration rate (eGFR) between 15-29 mL/min/1.73 m2 or <15 mL/min/1.73m² will be administered GLPG0634 100 mg once daily for 10 days	Drug: GLPG0634; 100 mg oral tablet, intake once daily for 10 days; Other Names: GLPG0634 tablets
Experimental: Part 1: Normal renal function; Part 1 - Group 2: subjects with normal renal function: eGFR ≥90 mL/min/1.73m² will be administered GLPG0634 100 mg once daily for 10 days	Drug: GLPG0634; 100 mg oral tablet, intake once daily for 10 days; Other Names: GLPG0634 tablets
Experimental: Part 2 - Mild renal impairment; Part 2 - Group 3: subjects with mild renal impairment: eGFR between 60-89 mL/min/1.73 m² will be administered GLPG0634 100 mg once daily for 10 days	Drug: GLPG0634; 100 mg oral tablet, intake once daily for 10 days; Other Names: GLPG0634 tablets
Experimental: Part 2 - Moderate renal impairment; Part 2 - Group 4:subjects with moderate renal impairment: eGFR between 30-59 mL/min/1.73 m² will be administered GLPG0634 100 mg once daily for 10 days	Drug: GLPG0634; 100 mg oral tablet, intake once daily for 10 days; Other Names: GLPG0634 tablets
Experimental: Part 2 - Normal renal function; Part 2 - Group 5: subjects with normal renal function: eGFR ≥90 mL/min/1.73 m² will be administered GLPG0634 100 mg once daily for 10 days	Drug: GLPG0634; 100 mg oral tablet, intake once daily for 10 days; Other Names: GLPG0634 tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed plasma concentration (Cmax)	Cmax of GLPG0634 and its metabolite after single and multiple dosing in subjects with renal impairment versus subjects with normal renal function	Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)
Area under the plasma drug concentration-time curve over 24 hours (AUC0-24h)	AUC0-24h of GLPG0634 and its metabolite after single and multiple dosing in subjects with renal impairment versus subjects with normal renal function	Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative amount excreted in urine expressed in μg and % of the dose administered (Ae)	Ae of GLPG0634 and its metabolite after single and multiple dosing in subjects with renal impairment versus subjects with normal renal function	Between dosing on Day 1 up to 48 h after dosing on Day 10 (Day 12)
Renal clearance (CLR)	CLR (calculated as Ae/AUC, where Ae and AUC are calculated over the same interval) of GLPG0634 and its metabolite after single and multiple dosing in subjects with renal impairment versus subjects with normal renal function	Between dosing on Day 1 up to 48 h after dosing on Day 10 (Day 12)
Plasma concentration observed at 24 h post-dose (C24h)	C24h of GLPG0634 and its metabolite after single and multiple dosing in subjects with renal impairment versus subjects with normal renal function	Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)
Average plasma concentration (Cavg)	Cavg (calculated as AUC0-24h/24h) of GLPG0634 and its metabolite after single and multiple dosing in subjects with renal impairment versus subjects with normal renal function	Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)
Time of occurrence of Cmax (tmax)	Tmax of GLPG0634 and its metabolite after single and multiple dosing in subjects with renal impairment versus subjects with normal renal function	Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)
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)	AUC0-z of GLPG0634 and its metabolite after single and multiple dosing in subjects with renal impairment versus subjects with normal renal function	Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)
Area under the plasma drug concentration-time curve, extrapolated to infinity (AUC0-∞)	AUC0-∞ of GLPG0634 and its metabolite after single and multiple dosing in subjects with renal impairment versus subjects with normal renal function	Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)
Apparent terminal half-life (t1/2,λz)	t1/2,λz (calculated from (ln 2)/λz being the apparent terminal rate constant) of GLPG0634 and its metabolite after single and multiple dosing in subjects with renal impairment versus subjects with normal renal function	Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)
Metabolite over parent ratio of AUC0-24h (R)	R (metabolite over parent ratio of AUC0-24h) after single and multiple dosing in subjects with renal impairment versus subjects with normal renal function	Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)
Accumulation ratio (Rac)	Rac (calculated as AUC0-24h Day 10/AUC0-24h Day 1) after dosing in subjects with renal impairment versus subjects with normal renal function	Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)
The number of subjects with adverse events	To evaluate the safety and tolerability of GLPG0634 in subjects with renal impairment versus subjects with normal renal function in terms of adverse events (AEs)	From screening up to 10 days after last dose (Day 20)
The number of subjects with abnormal laboratory parameters	To evaluate the safety and tolerability of GLPG0634 in subjects with renal impairment versus subjects with normal renal function in terms of abnormal laboratory parameters	From screening up to 10 days after last dose (Day 20)
The number of subjects with abnormal vital signs	To evaluate the safety and tolerability of GLPG0634 in subjects with renal impairment versus subjects with normal renal function in terms of abnormal vital signs	From screening up to 10 days after last dose (Day 20)
The number of subjects with abnormal electrocardiogram (ECG)	To evaluate the safety and tolerability of GLPG0634 in subjects with renal impairment versus subjects with normal renal function in terms of abnormal electrocardiogram (ECG)	From screening up to 10 days after last dose (Day 20)
The number of subjects with abnormal physical examination	To evaluate the safety and tolerability of GLPG0634 in subjects with renal impairment versus subjects with normal renal function in terms of abnormal physical examination	From screening up to 10 days after last dose (Day 20)

Collaborators and Investigators

• Sponsor: Galapagos NV
• Investigators: Study Director: Pille Harrison, MD, Galapagos NV

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: March 9, 2014
• First Submitted That Met QC Criteria: March 9, 2014
• First Posted (Estimate): March 11, 2014

Study Record Updates

• Last Update Posted (Estimate): July 22, 2014
• Last Update Submitted That Met QC Criteria: July 21, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: GLPG0634-CL-106; 2013-004407-40 (EudraCT Number)