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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-000156-25 | EudraCT Number |
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| Name | Class |
|---|---|
| Lakefront Biotherapeutics NV | INDUSTRY |
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The primary objective of this study is to evaluate the pharmacokinetics (PK) of filgotinib and its metabolite, GS-829845, in participants with varying degrees of impaired hepatic function relative to matched, healthy controls.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Moderate Hepatic Impairment | Experimental | Participants with moderate hepatic impairment and matched healthy controls will receive a single dose of filgotinib on Day 1. |
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| Severe Hepatic Impairment | Experimental | Participants with severe hepatic impairment and matched healthy controls will receive a single dose of filgotinib on Day 1. |
|
| Mild Hepatic Impairment | Experimental | Participants with mild hepatic impairment and matched healthy controls will receive a single dose of filgotinib on Day 1. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Filgotinib | Drug | 100 mg tablet administered orally |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic (PK) Parameter: AUClast of Filgotinib | AUClast is defined as the concentration of drug from time zero to the last observable concentration. | Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1 |
| PK Parameter: AUClast of GS-829845 | AUClast is defined as the concentration of drug from time zero to the last observable concentration. GS-829845 is the primary metabolite of filgotinib. | Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1 |
| PK Parameter: AUCinf of Filgotinib | AUCinf is defined as the concentration of drug extrapolated to infinite time. | Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1 |
| PK Parameter: AUCinf of GS-829845 | AUCinf is defined as the concentration of drug extrapolated to infinite time. GS-829845 is the primary metabolite of filgotinib. | Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1 |
| PK Parameter: Cmax of Filgotinib | Cmax is defined as the maximum observed concentration of drug. | Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1 |
| PK Parameter: Cmax of GS-829845 | Cmax is defined as the maximum observed concentration of drug. GS-829845 is the primary metabolite of filgotinib. | Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Who Experienced Treatment-Emergent Adverse Events | Day 1 up to Day 31 | |
| Percentage of Participants Who Experienced Graded Laboratory Abnormalities | Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant. |
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Key Inclusion Criteria:
Eligible individuals will be male and nonpregnant, nonlactating females, aged 18 to 70 years (inclusive), body mass index (BMI) between 18 and 36 kg/m^2 (inclusive), with either impaired hepatic function or normal hepatic function.
Individuals will be current nonsmokers (no use of tobacco, nicotine-containing, or tetrahydrocannabinol [THC]-containing products within the last 14 days).
Individuals with hepatic impairment will be categorized by the Child-Pugh-Turcotte (CPT) classification system indicating hepatic impairment as follows:
Hepatic impairment must have been stable during the 3 months (90 days) prior to study drug. Each individual in the control group will be matched to a individual with impaired hepatic function by age (± 10 years), gender, and body mass index (± 15%).
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Gilead Study Director | Gilead Sciences | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Pharmacology of Miami | Miami | Florida | 33014 | United States | ||
| American Research Corporation at the Texas Liver Institute |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Result | Anderson K, Zheng H, Medzihradsky O, et al. THU0117 PHARMACOKINETICS AND SHORT-TERM SAFETY OF FILGOTINIB, A SELECTIVE JANUS KINASE 1 INHIBITOR, IN SUBJECTS WITH MODERATE HEPATIC IMPAIRMENT. Annals of the Rheumatic Diseases. 2019;78:331. |
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38 participants were screened. Per protocol, participants in adaptive Cohort 2 (severe hepatic impairment) and Cohort 3 (mild hepatic impairment) were not enrolled following review of safety and pharmacokinetic (PK) data from participants in Cohort 1 (moderate hepatic impairment).
Participants were enrolled at study sites in Germany, New Zealand, and United States. The first participant was screened on 03 April 2018. The last study visit occurred on 09 August 2018.
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| ID | Title | Description |
|---|---|---|
| FG000 | Moderate Hepatic Impairment | Participants with moderate hepatic impairment received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state. |
| FG001 | Healthy Control | Matched healthy control participants received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Moderate Hepatic Impairment | Participants with moderate hepatic impairment received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state. |
| BG001 | Healthy Control |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Pharmacokinetic (PK) Parameter: AUClast of Filgotinib | AUClast is defined as the concentration of drug from time zero to the last observable concentration. | The PK Analysis Set included all enrolled participants who received at least 1 dose of filgotinib and had at least 1 nonmissing postdose concentration value of filgotinib or its primary metabolite GS-829845 reported by the PK laboratory. | Posted | Mean | Standard Deviation | h*ng/mL | Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1 |
|
Day 1 up to Day 31
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Moderate Hepatic Impairment | Participants with moderate hepatic impairment received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Gilead Clinical Study Information Center | Gilead Sciences | 1-833-445-3230 (GILEAD-0) | GileadClinicalTrials@gilead.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 19, 2017 | Jun 17, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 10, 2018 | Jun 17, 2019 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
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| ID | Term |
|---|---|
| C584571 | GLPG0634 |
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| Day 1 up to Day 31 |
| San Antonio |
| Texas |
| 78215 |
| United States |
| APEX GmbH | Munich | 81241 | Germany |
| Auckland Clinical Studies Ltd. | Grafton | Auckland | 1010 | New Zealand |
Matched healthy control participants received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state.
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
|
Matched healthy control participants received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state. |
|
|
|
| Primary | PK Parameter: AUClast of GS-829845 | AUClast is defined as the concentration of drug from time zero to the last observable concentration. GS-829845 is the primary metabolite of filgotinib. | Participants in the PK Analysis Set were analyzed. | Posted | Mean | Standard Deviation | h*ng/mL | Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1 |
|
|
|
|
| Primary | PK Parameter: AUCinf of Filgotinib | AUCinf is defined as the concentration of drug extrapolated to infinite time. | Participants in the PK Analysis Set were analyzed. | Posted | Mean | Standard Deviation | h*ng/mL | Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1 |
|
|
|
|
| Primary | PK Parameter: AUCinf of GS-829845 | AUCinf is defined as the concentration of drug extrapolated to infinite time. GS-829845 is the primary metabolite of filgotinib. | Participants in the PK Analysis Set were analyzed. | Posted | Mean | Standard Deviation | h*ng/mL | Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1 |
|
|
|
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| Primary | PK Parameter: Cmax of Filgotinib | Cmax is defined as the maximum observed concentration of drug. | Participants in the PK Analysis Set were analyzed. | Posted | Mean | Standard Deviation | ng/mL | Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1 |
|
|
|
|
| Primary | PK Parameter: Cmax of GS-829845 | Cmax is defined as the maximum observed concentration of drug. GS-829845 is the primary metabolite of filgotinib. | Participants in the PK Analysis Set were analyzed. | Posted | Mean | Standard Deviation | ng/mL | Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1 |
|
|
|
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| Secondary | Percentage of Participants Who Experienced Treatment-Emergent Adverse Events | The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug. | Posted | Number | percentage of participants | Day 1 up to Day 31 |
|
|
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| Secondary | Percentage of Participants Who Experienced Graded Laboratory Abnormalities | Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant. | Participants in the Safety Analysis Set were analyzed. | Posted | Number | percentage of participants | Day 1 up to Day 31 |
|
|
|
| 0 |
| 10 |
| 0 |
| 10 |
| 3 |
| 10 |
| EG001 | Healthy Control | Matched healthy control participants received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state. | 0 | 10 | 0 | 10 | 1 | 10 |
| Chest discomfort | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Rash papular | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
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After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:
| D003240 |
| Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |