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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-002444-14 | EudraCT Number |
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The primary objective of this study is to evaluate the pharmacokinetics (PK) of selonsertib in participants with impaired hepatic function relative to matched, healthy controls.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Moderate hepatic impairment (Cohort 1) | Experimental | Participants with moderate hepatic impairment and matched healthy controls will receive a single dose of selonsertib on Day 1. |
|
| Severe hepatic impairment (Cohort 2) | Experimental | Participants with severe hepatic impairment and matched healthy controls will receive a single dose of selonsertib on Day 1. |
|
| Mild hepatic impairment (Cohort 3) | Experimental | Participants with mild hepatic impairment and matched healthy controls will receive a single dose of selonsertib on Day 1. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Selonsertib | Drug | 6 mg tablets administered orally in fed state |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic (PK) Parameter: AUCinf of Selonsertib and Its Metabolite GS-607509 | AUCinf is defined as the concentration of drug extrapolated to infinite time. | 0 (predose), 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1. Additional PK samples were collected at the Day 10 and 14 follow-up visits approximately the same time as the Day 1 predose sample. |
| PK Parameter: AUClast of Selonsertib and Its Metabolite GS-607509 | AUClast is defined as the concentration of drug from time zero to the last observable concentration. | 0 (predose), 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1. Additional PK samples were collected at the Day 10 and 14 follow-up visits approximately the same time as the Day 1 predose sample. |
| PK Parameter: Cmax of Selonsertib and Its Metabolite GS-607509 | Cmax is defined as the maximum concentration of drug. | 0 (predose), 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1. Additional PK samples were collected at the Day 10 and 14 follow-up visits approximately the same time as the Day 1 predose sample. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Experiencing Treatment-Emergent Study Drug-related Adverse Events (AEs) | An AE was any untoward medical occurrence in a clinical study participant which did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Treatment-emergent AEs were defined as events that met one of the following criteria: 1) Any AEs with an onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug; or 2) Any AEs leading to premature discontinuation of study drug. |
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Key Inclusion Criteria:
All participants:
Participants with impaired hepatic function:
Healthy participants (matched control):
Key Exclusion Criteria:
All participants:
Participants with impaired hepatic function:
Healthy participants (matched control):
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 |
|---|---|---|---|---|---|---|
| Denver | Colorado | United States | ||||
107 participants were screened. In the control groups (normal hepatic function), each participant was matched for age, gender, race, and body mass index with a participant in the hepatic impairment group. 22 total unique participants with normal hepatic function were enrolled in Cohorts 1, 2, and 3. 3 participants served as matched control in both Cohort 1 and 2. 1 participant served as a matched control in both Cohort 1 and 3. 4 participants served as matched control in both Cohort 2 and 3.
Participants were enrolled at study sites in United States. The first participant was screened on 17 August 2015. The last study visit occurred on 15 December 2015.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1: Moderate Hepatic Impairment | Participants with moderate hepatic impairment received a single oral dose of selonsertib 6 mg (1 × 6 mg tablet) in fed state on Day 1. |
| FG001 | Cohort 2: Severe Hepatic Impairment | Participants with severe hepatic impairment received a single oral dose of selonsertib 6 mg (1 × 6 mg tablet) in fed state on Day 1. |
| FG002 | Cohort 3: Mild Hepatic Impairment | Participants with mild hepatic impairment received a single oral dose of selonsertib 6 mg (1 × 6 mg tablet) in fed state on Day 1. |
| FG003 | Healthy Control | Matched normal hepatic function participants received a single oral dose of selonsertib 6 mg (1 × 6 mg tablet) in fed state on Day 1. |
| 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 | Cohort 1: Moderate Hepatic Impairment | Participants with moderate hepatic impairment received a single oral dose of selonsertib 6 mg (1 × 6 mg tablet) in fed state on Day 1. |
| BG001 | Cohort 2: Severe Hepatic Impairment |
| 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: AUCinf of Selonsertib and Its Metabolite GS-607509 | AUCinf is defined as the concentration of drug extrapolated to infinite time. | PK Analysis Set included all enrolled participants who received at least 1 dose of selonsertib and had at least 1 evaluable PK concentration data value reported by the PK laboratory for the respective analytes. 3 participants served as matched control in both Cohort 1 and 2. 1 participant served as a matched control in both Cohort 1 and 3. 4 participants served as matched control in both Cohort 2 and 3. | Posted | Mean | Standard Deviation | hr*ng/mL | 0 (predose), 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1. Additional PK samples were collected at the Day 10 and 14 follow-up visits approximately the same time as the Day 1 predose sample. |
|
Day 1 plus 30 days
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 | Cohort 1: Moderate Hepatic Impairment | Participants with moderate hepatic impairment received a single oral dose of selonsertib 6 mg (1 × 6 mg tablet) in fed state on Day 1. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 18.1 | 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 |
| ID | Term |
|---|---|
| D003928 | Diabetic Nephropathies |
| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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| ID | Term |
|---|---|
| C000654501 | selonsertib |
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|
| Day 1 plus 30 days |
| Percentage of Participants Experiencing Any Treatment-Emergent and Grade ≥ 3 Laboratory Abnormalities | Treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from predose at any postdose visit, up to and including the date of last dose of study drug plus 30 days for participants who permanently discontinued study drug. If the relevant baseline laboratory value was missing, then any abnormality of at least Grade 1 observed within the time frame specified above was considered treatment-emergent. Severity grades were defined based on modified Common Terminology Criteria for Adverse Events (CTCAE) Laboratory Abnormality and Adverse Event Severity Grading, where 1=Mild, 2=Moderate, 3=Severe, 4=Potentially Life Threatening. The most severe graded abnormality from all tests was counted for each participant. | Day 1 plus 30 days |
| Miami |
| Florida |
| United States |
| Orlando | Florida | United States |
| Minneapolis | Minnesota | United States |
| San Antonio | Texas | United States |
Participants with severe hepatic impairment received a single oral dose of selonsertib 6 mg (1 × 6 mg tablet) in fed state on Day 1.
| BG002 | Cohort 3: Mild Hepatic Impairment | Participants with mild hepatic impairment received a single oral dose of selonsertib 6 mg (1 × 6 mg tablet) in fed state on Day 1. |
| BG003 | Healthy Control | Matched normal hepatic function participants received a single oral dose of selonsertib 6 mg (1 × 6 mg tablet) in fed state on Day 1. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants | No |
|
| Race (NIH/OMB) | Count of Participants | Participants | No |
|
Participants with moderate hepatic impairment received a single oral dose of selonsertib 6 mg (1 × 6 mg tablet) in fed state on Day 1.
| OG001 | Cohort 2: Severe Hepatic Impairment | Participants with severe hepatic impairment received a single oral dose of selonsertib 6 mg (1 × 6 mg tablet) in fed state on Day 1. |
| OG002 | Cohort 3: Mild Hepatic Impairment | Participants with mild hepatic impairment received a single oral dose of selonsertib 6 mg (1 × 6 mg tablet) in fed state on Day 1. |
| OG003 | Matched Healthy Control for Cohort 1 | Matched normal hepatic function participants to moderate hepatic impairment received a single oral dose of selonsertib 6 mg (1 × 6 mg tablet) in fed state on Day 1. |
| OG004 | Matched Healthy Control for Cohort 2 | Matched normal hepatic function participants to severe hepatic impairment received a single oral dose of selonsertib 6 mg (1 × 6 mg tablet) in fed state on Day 1. |
| OG005 | Matched Healthy Control for Cohort 3 | Matched normal hepatic function participants to mild hepatic impairment received a single oral dose of selonsertib 6 mg (1 × 6 mg tablet) in fed state on Day 1. |
|
|
|
| Primary | PK Parameter: AUClast of Selonsertib and Its Metabolite GS-607509 | AUClast is defined as the concentration of drug from time zero to the last observable concentration. | Participants in the PK Analysis Set were analyzed. 3 participants served as matched control in both Cohort 1 and 2. 1 participant served as a matched control in both Cohort 1 and 3. 4 participants served as matched control in both Cohort 2 and 3. | Posted | Mean | Standard Deviation | hr*ng/mL | 0 (predose), 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1. Additional PK samples were collected at the Day 10 and 14 follow-up visits approximately the same time as the Day 1 predose sample. |
|
|
|
|
| Primary | PK Parameter: Cmax of Selonsertib and Its Metabolite GS-607509 | Cmax is defined as the maximum concentration of drug. | Participants in the PK Analysis Set were analyzed. 3 participants served as matched control in both Cohort 1 and 2. 1 participant served as a matched control in both Cohort 1 and 3. 4 participants served as matched control in both Cohort 2 and 3. | Posted | Mean | Standard Deviation | ng/mL | 0 (predose), 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1. Additional PK samples were collected at the Day 10 and 14 follow-up visits approximately the same time as the Day 1 predose sample. |
|
|
|
|
| Secondary | Percentage of Participants Experiencing Treatment-Emergent Study Drug-related Adverse Events (AEs) | An AE was any untoward medical occurrence in a clinical study participant which did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Treatment-emergent AEs were defined as events that met one of the following criteria: 1) Any AEs with an onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug; or 2) Any AEs leading to premature discontinuation of study drug. | The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug. | Posted | Number | percentage of participants | Day 1 plus 30 days |
|
|
|
| Secondary | Percentage of Participants Experiencing Any Treatment-Emergent and Grade ≥ 3 Laboratory Abnormalities | Treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from predose at any postdose visit, up to and including the date of last dose of study drug plus 30 days for participants who permanently discontinued study drug. If the relevant baseline laboratory value was missing, then any abnormality of at least Grade 1 observed within the time frame specified above was considered treatment-emergent. Severity grades were defined based on modified Common Terminology Criteria for Adverse Events (CTCAE) Laboratory Abnormality and Adverse Event Severity Grading, where 1=Mild, 2=Moderate, 3=Severe, 4=Potentially Life Threatening. 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 plus 30 days |
|
|
|
| 0 |
| 10 |
| 3 |
| 10 |
| EG001 | Cohort 2: Severe Hepatic Impairment | Participants with severe hepatic impairment received a single oral dose of selonsertib 6 mg (1 × 6 mg tablet) in fed state on Day 1. | 0 | 10 | 0 | 10 |
| EG002 | Cohort 3: Mild Hepatic Impairment | Participants with mild hepatic impairment received a single oral dose of selonsertib 6 mg (1 × 6 mg tablet) in fed state on Day 1. | 0 | 10 | 2 | 10 |
| EG003 | Healthy Control | Matched normal hepatic function participants received a single oral dose of selonsertib 6 mg (1 × 6 mg tablet) in fed state on Day 1. | 0 | 22 | 2 | 22 |
| Dry mouth | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 18.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
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:
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D048909 | Diabetes Complications |
| D003920 | Diabetes Mellitus |
| D004700 | Endocrine System Diseases |
| AUClast of GS-607509 |
|
| % GLSM ratio |
| 141.75 |
| 2-Sided |
| 90 |
| 118.50 |
| 169.55 |
| Other |
| AUClast of selonsertib | % GLSM ratio | 112.24 | 2-Sided | 90 | 87.69 | 143.65 | Other |
| AUClast of GS-607509 | % GLSM ratio | 61.20 | 2-Sided | 90 | 43.06 | 86.98 | Other |
| AUClast of GS-607509 | % GLSM ratio | 61.07 | 2-Sided | 90 | 33.62 | 110.91 | Other |
| AUClast of GS-607509 | % GLSM ratio | 96.13 | 2-Sided | 90 | 48.47 | 190.67 | Other |
| Cmax of GS-607509 |
|
| % GLSM ratio |
| 91.16 |
| 2-Sided |
| 90 |
| 78.76 |
| 105.52 |
| Other |
| Cmax of selonsertib | % GLSM ratio | 100.19 | 2-Sided | 90 | 83.73 | 119.88 | Other |
| Cmax of GS-607509 | % GLSM ratio | 71.44 | 2-Sided | 90 | 54.58 | 93.50 | Other |
| Cmax of GS-607509 | % GLSM ratio | 46.92 | 2-Sided | 90 | 32.59 | 67.54 | Other |
| Cmax of GS-607509 | % GLSM ratio | 93.93 | 2-Sided | 90 | 67.60 | 130.50 | Other |
| Grade ≥ 3 Laboratory Abnormalities |
|