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

Renal Impairment Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02084199
• Other study ID #: GLPG0634-CL-106
• Secondary ID: 2013-004407-40
• Status: Completed
• Phase: Phase 1
• First received: March 9, 2014
• Last updated: July 21, 2014
• Start date: March 2014
• Est. completion date: July 2014

Study information

• Verified date: July 2014
• Source: Galapagos NV
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 79 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Renal Impairment
• Renal Insufficiency

Intervention

Drug:
• GLPG0634
100 mg oral tablet, intake once daily for 10 days

Locations

Country	Name	City	State
Germany	CRS Clinical Research Services Kiel GmbH	Kiel

Sponsors (1)

Lead Sponsor	Collaborator
Galapagos NV

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Primary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	Area under the plasma drug concentration-time curve, extrapolated to infinity (AUC0-8)	AUC0-8 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)	No
Secondary	Apparent terminal half-life (t1/2,?z)	t1/2,?z (calculated from (ln 2)/?z 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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes