Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2016-003266-98 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The primary objective of this study is to evaluate the pharmacokinetics of entospletinib (ENTO) and/or its metabolites (if applicable) in participants with impaired hepatic function (stratified by smoking status, as appropriate) relative to matched, healthy controls.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 (Moderate Hepatic Impairment) | Experimental | Entospletinib administered twice daily on Days 1-4, and 1 morning dose only on Day 5. |
|
| Cohort 2 (Severe Hepatic Impairment) | Experimental | Entospletinib administered twice daily on Days 1-4, and 1 morning dose only on Day 5. |
|
| Cohort 3 (Mild Hepatic Impairment) | Experimental | Entospletinib administered twice daily on Days 1-4, and 1 morning dose only on Day 5. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Entospletinib | Drug | Entospletinib 100 mg tablet administered orally |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic (PK) Parameter: AUCtau of ENTO | AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). | 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60, 72, 84, and 96 hours postdose on Day 5 |
| Pharmacokinetic (PK) Parameter: Cmax of ENTO | Cmax is defined as the maximum concentration of drug. | 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60, 72, 84, and 96 hours postdose on Day 5 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | TEAEs are defined as events that meet one of the following criteria:
| Baseline up to Day 9 plus 30 days |
Not provided
Key Inclusion Criteria:
Key Exclusion Criteria:
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Gilead Study Director | Gilead Sciences | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Pharmacology of Miami, Inc. (CPMI) | Miami | Florida | United States | |||
| Orlando Clinical Research Center |
102 participants were screened.
Participants were enrolled at study sites in United States, New Zealand, and Germany. The first participant was screened on 16 November 2015. The last study visit occurred on 25 October 2017.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Severe Hepatic Impairment | Participants with severe hepatic impairment received entospletinib (ENTO) 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5. |
| FG001 | Moderate Hepatic Impairment | Participants with moderate hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5. |
| FG002 | Mild Hepatic Impairment | Participants with mild hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5. |
| FG003 | Healthy Control | Participants with normal hepatic function received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Severe Hepatic Impairment | Participants with severe hepatic impairment received entospletinib (ENTO) 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5. |
| BG001 | Moderate 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: AUCtau of ENTO | AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). | Participants in the PK Analysis Set (all enrolled participants who received at least one dose of ENTO and had at least one evaluable PK concentration data value reported by the PK lab) with available data were analyzed. Healthy control participants may participate in more than one cohorts. | Posted | Mean | Standard Deviation | h*ng/mL | 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60, 72, 84, and 96 hours postdose on Day 5 |
|
First dose date up to Day 9 plus 30 days
Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Severe Hepatic Impairment | Participants with severe hepatic impairment received entospletinib (ENTO) 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal distension | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Gilead Clinical Study Information Center | Gilead Sciences | 1-833-445-3230 (GILEAD-0) | GileadClinicalTrials@gilead.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol: Original | Jul 28, 2015 | May 6, 2019 | Prot_000.pdf |
| Prot | Yes | No | No | Study Protocol: Amendment 1 | Oct 16, 2015 | May 6, 2019 | Prot_001.pdf |
| Prot | Yes | No | No | Study Protocol: Amendment 2 | Jul 1, 2016 | May 7, 2019 | Prot_002.pdf |
| Prot | Yes | No | No | Study Protocol: Amendment 3 | Aug 26, 2016 | May 7, 2019 | Prot_003.pdf |
| Prot | Yes | No | No | Study Protocol: Amendment 4 | Nov 30, 2016 | May 7, 2019 | Prot_004.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 30, 2018 | May 7, 2019 | SAP_005.pdf |
Not provided
| ID | Term |
|---|---|
| D009369 | Neoplasms |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| C000589391 | 6-(1H-indazol-6-yl)-N-(4-morpholinophenyl)imidazo(1,2-a)pyrazin-8-amine |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Percentage of Participants Experiencing Treatment-Emergent 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 subject. | Baseline up to Day 9 plus 30 days |
| Orlando |
| Florida |
| United States |
| DaVita Clinical Research | Minneapolis | Minnesota | United States |
| The Texas Liver Institute | San Antonio | Texas | United States |
| APEX GmBH | Munich | Germany |
| Auckland Clinical Studies | Auckland | New Zealand |
Participants with moderate hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.
| BG002 | Mild Hepatic Impairment | Participants with mild hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5. |
| BG003 | Healthy Control | Participants with normal hepatic function received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | Cohort 1: Moderate Hepatic Impairment Non-smoking | Participants with moderate hepatic impairment who are non-smokers received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5. |
| OG002 | Cohort 1: Healthy Control Matched to Smoking | Participants with normal hepatic function who are smokers received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5. |
| OG003 | Cohort 1: Healthy Control Matched to Non-smoking | Participants with normal hepatic function who are non-smokers received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5. |
| OG004 | Cohort 2: Severe Hepatic Impairment | Participants with severe hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5. |
| OG005 | Cohort 2: Healthy Control | Participants with normal hepatic function received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5. |
| OG006 | Cohort 3: Mild Hepatic Impairment | Participants with mild hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5. |
| OG007 | Cohort 3: Healthy Control | Participants with normal hepatic function received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5. |
|
|
|
| Primary | Pharmacokinetic (PK) Parameter: Cmax of ENTO | Cmax is defined as the maximum concentration of drug. | Participants in the PK Analysis Set with available data were analyzed. Healthy control participants may participate in more than one cohorts. | Posted | Mean | Standard Deviation | ng/mL | 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60, 72, 84, and 96 hours postdose on Day 5 |
|
|
|
|
| Secondary | Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | TEAEs are defined as events that meet one of the following criteria:
| Safety Analysis Set included all randomized participants who received at least one dose of study drug. | Posted | Number | percentage of participants | Baseline up to Day 9 plus 30 days |
|
|
|
| Secondary | Percentage of Participants Experiencing Treatment-Emergent 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 subject. | Participants in the Safety Analysis Set were analyzed. | Posted | Number | percentage of participants | Baseline up to Day 9 plus 30 days |
|
|
|
| 0 |
| 7 |
| 0 |
| 7 |
| 1 |
| 7 |
| EG001 | Moderate Hepatic Impairment | Participants with moderate hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5. | 0 | 18 | 0 | 18 | 4 | 18 |
| EG002 | Mild Hepatic Impairment | Participants with mild hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5. | 0 | 10 | 0 | 10 | 3 | 10 |
| EG003 | Healthy Control | Participants with normal hepatic function received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5. | 0 | 20 | 0 | 20 | 6 | 20 |
| Constipation | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Infected bite | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Laceration | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Muscle tightness | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Chromaturia | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA 20.1 | 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:
| 211.94 |
| 2-Sided |
| 90 |
| 132.49 |
| 339.03 |
| Other |
| GMR | 171.33 | 2-Sided | 90 | 108.17 | 271.37 | Other |
| GMR | 107.35 | 2-Sided | 90 | 72.71 | 158.51 | Other |