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

Primary Purpose

Renal Impairment

Status

Completed

Phase

Phase 1

Locations

Germany

Study Type

Interventional

Intervention

GLPG0634

About this trial

This is an interventional treatment trial for Renal Impairment

Eligibility Criteria

18 Years - 79 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

CRS Clinical Research Services Kiel GmbH

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

Part 1 - Severe renal impairment

Part 1: Normal renal function

Part 2 - Mild renal impairment

Part 2 - Moderate renal impairment

Part 2 - Normal renal function

Arm Description

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

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

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

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

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

Outcomes

Primary Outcome Measures

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

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

Secondary Outcome Measures

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

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

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

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

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

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

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

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

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

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

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)

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

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

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)

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

Full Information

NCT ID

NCT02084199

First Posted

March 9, 2014

Last Updated

July 21, 2014

Sponsor

Galapagos NV

1. Study Identification

Unique Protocol Identification Number

NCT02084199

Brief Title

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

2. Study Status

Record Verification Date

July 2014

Overall Recruitment Status

Completed

Study Start Date

March 2014 (undefined)

Primary Completion Date

July 2014 (Actual)

Study Completion Date

July 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Galapagos NV

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Renal Impairment

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1 - Severe renal impairment

Arm Type

Experimental

Arm Description

Arm Title

Part 1: Normal renal function

Arm Type

Experimental

Arm Description

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

Arm Title

Part 2 - Mild renal impairment

Arm Type

Experimental

Arm Description

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

Arm Title

Part 2 - Moderate renal impairment

Arm Type

Experimental

Arm Description

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

Arm Title

Part 2 - Normal renal function

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

GLPG0634

Other Intervention Name(s)

GLPG0634 tablets

Intervention Description

100 mg oral tablet, intake once daily for 10 days

Primary Outcome Measure Information:

Title

Maximum observed plasma concentration (Cmax)

Description

Cmax of GLPG0634 and its metabolite after single and multiple dosing in subjects with renal impairment versus subjects with normal renal function

Time Frame

Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)

Title

Area under the plasma drug concentration-time curve over 24 hours (AUC0-24h)

Description

AUC0-24h of GLPG0634 and its metabolite after single and multiple dosing in subjects with renal impairment versus subjects with normal renal function

Time Frame

Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)

Secondary Outcome Measure Information:

Title

Cumulative amount excreted in urine expressed in μg and % of the dose administered (Ae)

Description

Ae of GLPG0634 and its metabolite after single and multiple dosing in subjects with renal impairment versus subjects with normal renal function

Time Frame

Between dosing on Day 1 up to 48 h after dosing on Day 10 (Day 12)

Title

Renal clearance (CLR)

Description

Time Frame

Between dosing on Day 1 up to 48 h after dosing on Day 10 (Day 12)

Title

Plasma concentration observed at 24 h post-dose (C24h)

Description

C24h of GLPG0634 and its metabolite after single and multiple dosing in subjects with renal impairment versus subjects with normal renal function

Time Frame

Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)

Title

Average plasma concentration (Cavg)

Description

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

Time Frame

Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)

Title

Time of occurrence of Cmax (tmax)

Description

Tmax of GLPG0634 and its metabolite after single and multiple dosing in subjects with renal impairment versus subjects with normal renal function

Time Frame

Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)

Title

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)

Description

AUC0-z of GLPG0634 and its metabolite after single and multiple dosing in subjects with renal impairment versus subjects with normal renal function

Time Frame

Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)

Title

Area under the plasma drug concentration-time curve, extrapolated to infinity (AUC0-∞)

Description

AUC0-∞ of GLPG0634 and its metabolite after single and multiple dosing in subjects with renal impairment versus subjects with normal renal function

Time Frame

Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)

Title

Apparent terminal half-life (t1/2,λz)

Description

Time Frame

Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)

Title

Metabolite over parent ratio of AUC0-24h (R)

Description

R (metabolite over parent ratio of AUC0-24h) after single and multiple dosing in subjects with renal impairment versus subjects with normal renal function

Time Frame

Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)

Title

Accumulation ratio (Rac)

Description

Rac (calculated as AUC0-24h Day 10/AUC0-24h Day 1) after dosing in subjects with renal impairment versus subjects with normal renal function

Time Frame

Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)

Title

The number of subjects with adverse events

Description

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)

Time Frame

From screening up to 10 days after last dose (Day 20)

Title

The number of subjects with abnormal laboratory parameters

Description

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

Time Frame

From screening up to 10 days after last dose (Day 20)

Title

The number of subjects with abnormal vital signs

Description

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

Time Frame

From screening up to 10 days after last dose (Day 20)

Title

The number of subjects with abnormal electrocardiogram (ECG)

Description

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)

Time Frame

From screening up to 10 days after last dose (Day 20)

Title

The number of subjects with abnormal physical examination

Description

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

Time Frame

From screening up to 10 days after last dose (Day 20)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

79 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pille Harrison, MD

Organizational Affiliation

Galapagos NV

Official's Role

Study Director

Facility Information:

Facility Name

CRS Clinical Research Services Kiel GmbH

City

Kiel

Country

Germany

12. IPD Sharing Statement

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

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