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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-004426-18 | EudraCT Number |
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The primary objective of this study is to evaluate the single-dose pharmacokinetics of tenofovir alafenamide (TAF) and its metabolite tenofovir (TFV) in participants with normal hepatic function and in participants with severe hepatic impairment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Severe Hepatic Impairment Group | Experimental | Participants with severe hepatic impairment will receive a single oral dose of TAF 25 mg on Day 1. |
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| Matched Normal Hepatic Function Group | Active Comparator | Participants with normal hepatic function will receive a single oral dose of TAF 25 mg on Day 1. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TAF | Drug | 25 mg tablet administered orally |
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| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic (PK) Parameter: AUCinf of Tenofovir Alafenamide (TAF), Its Metabolite Tenofovir (TFV) and Free (Unbound) TAF | AUCinf is defined as the concentration of drug extrapolated to infinite time. | Predose (≤5 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 12, 24, 36, 48, 60, 72, 96, 120, and 144 hours postdose on Day 1 |
| PK Parameter: Cmax of TAF, Its Metabolite TFV and Free (Unbound) TAF | Cmax is defined as the maximum concentration of drug. | Predose (≤5 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 12, 24, 36, 48, 60, 72, 96, 120, and 144 hours postdose on Day 1 |
| PK Parameter: AUClast of TAF, Its Metabolite TFV and Free (Unbound) TAF | AUClast is defined as the concentration of drug from time zero to the last observable concentration. | Predose (≤5 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 12, 24, 36, 48, 60, 72, 96, 120, and 144 hours postdose on Day 1 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | TEAEs are events that meet one of the following criteria: any AEs with onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug or any AEs leading to premature discontinuation of study drug. | Day 1 plus 30 days |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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 |
|---|---|---|---|---|---|---|
| Miami | Florida | 33014 | United States | |||
Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy
18 months after study completion
A secured external environment with username, password, and RSA code.
28 participants were screened.
Participants were enrolled at study sites in Germany, New Zealand, and the United States. The first participant was screened on 22 December 2014. The last study visit occurred on 17 April 2015.
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| ID | Title | Description |
|---|---|---|
| FG000 | Severe Hepatic Impairment Group | Participants with severe hepatic impairment received a single oral dose of tenofovir alafenamide (TAF) 25 mg on Day 1. |
| FG001 | Matched Normal Hepatic Function Group |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| 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. These were graded as Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening. The most severe graded abnormality from all tests was counted for each participant. | Day 1 plus 30 days |
| Orlando |
| Florida |
| 32809 |
| United States |
| San Antonio | Texas | 78215 | United States |
| Munich | D-81241 | Germany |
| Gratton | Auckland | 1142 | New Zealand |
Participants with normal hepatic function received a single oral dose of TAF 25 mg on Day 1.
| COMPLETED |
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| NOT COMPLETED |
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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 | Severe Hepatic Impairment Group | Participants with severe hepatic impairment received a single oral dose of TAF 25 mg on Day 1. |
| BG001 | Matched Normal Hepatic Function Group | Participants with normal hepatic function received a single oral dose of TAF 25 mg on Day 1. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants | No |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants | No |
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| Race (NIH/OMB) | Count of Participants | Participants | No |
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| Region of Enrollment | Number | participants |
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| 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Pharmacokinetic (PK) Parameter: AUCinf of Tenofovir Alafenamide (TAF), Its Metabolite Tenofovir (TFV) and Free (Unbound) TAF | AUCinf is defined as the concentration of drug extrapolated to infinite time. | Participants in the PK Analysis Set (consisted of all enrolled participants who received at least 1 dose of the study drug and had at least 1 non-missing PK concentration data for each respective analyte) with available data were analyzed. | Posted | Mean | Standard Deviation | h*ng/mL | Predose (≤5 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 12, 24, 36, 48, 60, 72, 96, 120, and 144 hours postdose on Day 1 |
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| Primary | PK Parameter: Cmax of TAF, Its Metabolite TFV and Free (Unbound) TAF | Cmax is defined as the maximum concentration of drug. | Participants in the PK Analysis Set were analyzed. | Posted | Mean | Standard Deviation | ng/mL | Predose (≤5 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 12, 24, 36, 48, 60, 72, 96, 120, and 144 hours postdose on Day 1 |
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| Primary | PK Parameter: AUClast of TAF, Its Metabolite TFV and Free (Unbound) TAF | AUClast is defined as the concentration of drug from time zero to the last observable concentration. | Participants in the PK Analysis Set were analyzed. | Posted | Mean | Standard Deviation | h*ng/mL | Predose (≤5 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 12, 24, 36, 48, 60, 72, 96, 120, and 144 hours postdose on Day 1 |
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| Secondary | Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | TEAEs are events that meet one of the following criteria: any AEs with onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug or 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 |
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| 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. These were graded as Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: 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 |
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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 | Severe Hepatic Impairment Group | Participants with severe hepatic impairment received a single oral dose of TAF 25 mg on Day 1. | 0 | 10 | 1 | 10 | 4 | 10 |
| EG001 | Matched Normal Hepatic Function Group | Participants with normal hepatic function received a single oral dose of TAF 25 mg of on Day 1. | 0 | 10 | 0 | 10 | 3 | 10 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hepatic failure | Hepatobiliary disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal distension | Gastrointestinal disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA Version 18.0 | 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:
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Gilead Clinical Study Information Center | Gilead Sciences | 1-833-445-3230 (GILEAD-0) | GileadClinicalTrials@gilead.com |
| ID | Term |
|---|---|
| D006509 | Hepatitis B |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D018347 | Hepadnaviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D006525 | Hepatitis, Viral, Human |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| New Zealand |
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| United States |
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| Free (unbound) TAF |
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| TFV: Severe Hepatic Impairment Group vs. Matched Normal Hepatic Function Group | GLSM ratio percentage | 63.06 | 2-Sided | 90 | 42.90 | 92.70 | Equivalence | Sample size calculations were done in Query Advisor 6.0 by using the "Two-group t-test of equal means (equal n's)" module with α (one-sided) = 0.05, upper equivalence limit = ln(2.0) = 0.691, and expected difference = 0. |
| Free (unbound) TAF: Severe Hepatic Impairment Group vs. Matched Normal Hepatic Function Group | GLSM ratio percentage | 94.42 | 2-Sided | 90 | 72.48 | 122.99 | Equivalence | Sample size calculations were done in Query Advisor 6.0 by using the "Two-group t-test of equal means (equal n's)" module with α (one-sided) = 0.05, upper equivalence limit = ln(2.0) = 0.691, and expected difference = 0. |
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