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| Name | Class |
|---|---|
| GlaxoSmithKline | INDUSTRY |
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The abacavir (ABC)/dolutegravir (DTG)/lamivudine (3TC) 600 milligrams (mg)/50 mg/300 mg fixed-dose combination (FDC) tablet is currently approved in the United States (US) and Europe. Although the pharmacokinetics (PK), safety and tolerability of ABC/DTG/3TC FDC tablets have been extensively studied in subjects not of Japanese heritage, these parameters have not been exclusively assessed in Japanese subjects. To support the marketing application in Japan, this single-dose, open-label study will characterize the PK, safety and tolerability of ABC/DTG/3TC FDC tablet in adult Japanese healthy subjects. A maximum of 12 subjects will be enrolled such that approximately 10 evaluable subjects complete the study. The study will consist of a screening, treatment phase (single oral dose under the fasted state) and follow-up visit (within 7-14 days of the last PK sample collected). The total duration of the study for each subject will be approximately up to 48 days.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ABC/DTG/3TC FDC | Experimental | Each subject will receive treatment with a single oral dose of ABC 600 mg/DTG 50 mg/3TC 300 mg FDC tablet administered under the fasted state |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ABC/DTG/3TC FDC tablet | Drug | ABC/DTG/3TC FDC will be supplied as purple, biconvex, oval tablets debossed with "572 Trı" on one side and plain on the other side. A single dose, with a unit dose strength of 600 mg/50 mg/300 mg will be administered orally. |
| Measure | Description | Time Frame |
|---|---|---|
| Area under the concentration-time curve from time zero (pre-dose) to time of last quantifiable concentration (AUC[0-t]) following a single oral dose administration of ABC/DTG/3TC 600 mg/ 50 mg/ 300 mg FDC tablet in healthy, adult Japanese subjects | Blood samples for PK analyses will be collected at pre-dose and 30 minutes, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post- dose. | Day 1: Pre-dose and at 30 minutes, 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 12 h, 16 h, 24 h, 36 h, 48 h and 72 h post dose. |
| Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-infinity]) following a single oral dose administration of ABC/DTG/3TC 600 mg/ 50 mg/ 300 mg FDC tablet in healthy, adult Japanese subjects | Blood samples for PK analyses will be collected at pre-dose and 30 minutes, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post- dose. | Day 1: Pre-dose and at 30 minutes, 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 12 h, 16 h, 24 h, 36 h, 48 h and 72 h post dose. |
| Maximum observed plasma concentration (Cmax) following a single oral dose administration of ABC/DTG/3TC 600 mg/ 50 mg/ 300 mg FDC tablet in healthy, adult Japanese subjects | Blood samples for PK analyses will be collected at pre-dose and 30 minutes, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post- dose. | Day 1: Pre-dose and at 30 minutes, 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 12 h, 16 h, 24 h, 36 h, 48 h and 72 h post dose. |
| Time of occurrence of Cmax (tmax) following a single oral dose administration of ABC/DTG/3TC 600 mg/ 50 mg/ 300 mg FDC tablet in healthy, adult Japanese subjects | Blood samples for PK analyses will be collected at pre-dose and 30 minutes, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post- dose. | Day 1: Pre-dose and at 30 minutes, 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 12 h, 16 h, 24 h, 36 h, 48 h and 72 h post dose. |
| Measure | Description | Time Frame |
|---|---|---|
| Safety as assessed by the number of subjects with adverse events (AE) and serious adverse events (SAE) | An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. | From Day-1 up to follow-up (approx. Day 18) |
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Inclusion Criteria:
Females- A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum or urine [according to the sites standard of practice] human chorionic gonadotrophin [hCG] test), not lactating, and at least one of the following conditions applies:
The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
Exclusion Criteria:
NOTES:
The QT duration corrected for heart rate (QTc) is the QTcF machine-read or manually over-read.
The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trial.
For purposes of data analysis, QT interval corrected for heart rate using Bazett's formula (QTcB), QTcF, another QT correction formula, or a composite of available values of QTc will be used as specified in the reporting and analysis plan (RAP).
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | ViiV Healthcare | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Glendale | California | 91206 | United States |
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| Concentration at 24 h after dose administration (C24) following a single oral dose administration of ABC/DTG/3TC 600 mg/ 50 mg/ 300 mg FDC tablet in healthy, adult Japanese subjects | Blood samples for PK analyses will be collected at pre-dose and 30 minutes, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post- dose. | Day 1: Pre-dose and at 30 minutes, 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 12 h, 16 h, 24 h, 36 h, 48 h and 72 h post dose. |
| Terminal phase half-time (t1/2) following a single oral dose administration of ABC/DTG/3TC 600 mg/ 50 mg/ 300 mg FDC tablet in healthy, adult Japanese subjects | Blood samples for PK analyses will be collected at pre-dose and 30 minutes, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post- dose. | Day 1: Pre-dose and at 30 minutes, 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 12 h, 16 h, 24 h, 36 h, 48 h and 72 h post dose. |
| Apparent clearance following oral dosing (CL/F) following a single oral dose administration of ABC/DTG/3TC 600 mg/ 50 mg/ 300 mg FDC tablet in healthy, adult Japanese subjects | Blood samples for PK analyses will be collected at pre-dose and 30 minutes, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post- dose. | Day 1: Pre-dose and at 30 minutes, 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 12 h, 16 h, 24 h, 36 h, 48 h and 72 h post dose. |
| Percentage of AUC(0-infinity) obtained by extrapolation (%AUCex) following a single oral dose administration of ABC/DTG/3TC 600 mg/ 50 mg/ 300 mg FDC tablet in healthy, adult Japanese subjects | Blood samples for PK analyses will be collected at pre-dose and 30 minutes, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post- dose. | Day 1: Pre-dose and at 30 minutes, 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 12 h, 16 h, 24 h, 36 h, 48 h and 72 h post dose. |
| Terminal phase rate constant (Lambda-z) following a single oral dose administration of ABC/DTG/3TC 600 mg/ 50 mg/ 300 mg FDC tablet in healthy, adult Japanese subjects | Blood samples for PK analyses will be collected at pre-dose and 30 minutes, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post- dose. | Day 1: Pre-dose and at 30 minutes, 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 12 h, 16 h, 24 h, 36 h, 48 h and 72 h post dose. |
| Absolute values for composite of clinical chemistry parameters as a safety measure | Clinical chemistry parameters includes blood urea nitrogen, potassium, aspartate aminotransferase, total and direct bilirubin, creatinine, sodium, alanine aminotransferase, total protein, glucose, calcium, alkaline phosphatase and albumin | Day-1 and follow-up (approx. Day 18) |
| Change from baseline values for composite of clinical chemistry parameters as a safety measure | Clinical chemistry parameters includes blood urea nitrogen, potassium, aspartate aminotransferase, total and direct bilirubin, creatinine, sodium, alanine aminotransferase, total protein, glucose, calcium, alkaline phosphatase and albumin | Day-1 and follow-up (approx. Day 18) |
| Urinalysis assessments | Day-1 and follow-up (approx. Day 18) |
| Safety as assessed by systolic and diastolic blood pressure measurements | Day-1, pre-dose and at 4 h, 24 h, 48 h post-dose, and follow-up (approx. Day 18) |
| Safety as assessed by pulse rate measurements | Day-1, pre-dose and at 4 h, 24 h, 48 h post-dose, and follow-up (approx. Day 18) |
| Safety as assessed by 12-lead electrocardiogram (ECG) | Single 12-lead ECG will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT correction using Fridericia's Formula (QTcF) intervals. | Day-1 and follow-up (approx. Day 18) |
| Absolute values for composite of clinical haematology parameters as a safety measure | Clinical haematology parameters includes platelet count, red blood cell count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, neutrophils, lymphocytes, monocytes, eosinophils and basophils | Day-1 and follow-up (approx. Day 18) |
| Change from baseline values for composite of clinical haematology parameters as a safety measure | Clinical haematology parameters includes platelet count, red blood cell count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, neutrophils, lymphocytes, monocytes, eosinophils and basophils | Day-1 and follow-up (approx. Day 18) |
| ID | Term |
|---|---|
| D007239 | Infections |
| D000163 | Acquired Immunodeficiency Syndrome |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012897 | Slow Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
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