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| Name | Class |
|---|---|
| Shionogi | INDUSTRY |
The purpose of this study is to compare the amount of GSK1349572 (study drug) in the blood when given with and without atazanavir/ritonavir or atazanavir and to compare the blood levels of atazanavir when given with GSK1349572 to historical data for atazanavir.
GSK1349572 is an integrase inhibitor that will be evaluated for the treatment of HIV infection. As GSK1349572 progresses into clinical trials in HIV-infected patients where combination antiretroviral therapy is the standard of care, it is likely that it will be dosed with protease inhibitors (PIs) including atazanavir/ritonavir (ATV/RTV) and atazanavir alone. Ritonavir is a substrate of CYP3A and inhibitor of CYP3A and Pgp and atazanavir is an inhibitor of UGT1A1. Ritonavir is also a known inducer of CYP and UGT enzymes. As GSK1349572 likely undergoes metabolism by CYP and UGT enzymes and is a Pgp substrate, a drug interaction study between GSK1349572 and ATV is warranted. GSK1349572 is not an inhibitor or inducer of CYP3A and is not expected to have impact on pharmacokinetics (PK) of atazanavir and ritonavir. Accordingly, the primary objective of this study is to compare steady-state plasma PK, safety and tolerability of GSK1349572 30 mg every 24h (q24h) with and without ATV/RTV 300/100 mg q24h or ATV 400mg q24h.
Approximately 24 subjects will receive GSK1349572 30mg q24h for 5 days (Treatment A). Subjects will then be administered GSK1349572 30mg q24h in combination with either ATV/RTV 300/100 mg q24h (Treatment B, n=12) or ATV 400 mg q24h (Treatment C, n=12) for 14 days. There will be no washout between treatments. Safety evaluations and serial PK samples will be collected during each treatment period. A follow-up visit will occur 7-14 days after the last dose of study drug.
This study will be conducted at one center in the US, with healthy adult male and female subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequence 2 | Experimental | In the first treatment period, all subjects will receive GSK1349572 30mg q24h for 5 days (treatment A). In period two, subjects will receive GSK1349572 30mg q24h in combination with ATV 400mg q24h (treatment C) for 14 days. There will be no washout between treatment periods. Day 1 of Period 2 will be the day after Day 5 of Period 1. Subjects will have a screening visit within 30 days prior to the first dose of study drug, two treatment periods, and a follow-up visit 7-14 days after the last dose of study drug. |
|
| Sequence 1 | Experimental | In the first treatment period, all subjects will receive GSK1349572 30mg q24h for 5 days (treatment A). In period two, subjects will receive GSK1349572 30mg q24h in combination with ATV/RTV 300/100mg q24h (treatment B) for 14 days. There will be no washout between treatment periods. Day 1 of Period 2 will be the day after Day 5 of Period 1. Subjects will have a screening visit within 30 days prior to the first dose of study drug, two treatment periods, and a follow-up visit 7-14 days after the last dose of study drug. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK1349572 | Drug | GSK1349572 30 mg once a day for 5 days in Period 1 and 14 days in Period 2 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Plasma GSK1349572 steady-state AUC(0-tau), Cmax, C0, Ctau, and Cmin following administration of GSK1349572 30mg q24h for 5 days and following co-administration with ATV/RTV 300/100mg q24h or ATV 400mg q24h for 14 days. | 19 days |
| Measure | Description | Time Frame |
|---|---|---|
| Safety and tolerability parameters, including adverse event, concurrent medication, clinical laboratory, ECG, and vital signs assessments. | 19 days | |
| Plasma GSK1349572 PK parameters: tmax, tmin, CL/F and t½, following administration of GSK1349572 30mg q24h for 5 days and following co-administration with ATZ/RTV 300/100mg q24h or ATZ 400mg q24h for 14 days. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Austin | Texas | 78744 | United States |
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| ID | Term |
|---|---|
| C562325 | dolutegravir |
| D000069446 | Atazanavir Sulfate |
| D019438 | Ritonavir |
| ID | Term |
|---|---|
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009842 | Oligopeptides |
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| Atazanavir 300 mg | Drug | Atazanavir 300 mg once per day for 14 days in Period 2 |
|
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| Atazanavir 400 mg | Drug | Atazanavir 400 mg once a day for 14 days in Period 2 |
|
|
| Ritonavir | Drug | Ritonavir 100 mg once a day for 14 days in Period 2 |
|
|
| 19 days |
| Plasma ATV PK parameters, including AUC(0-tau), Cmax, Ctau, and Cmin following co-administration of GSK1349572 30mg q24h and ATV/RTV 300/100mg q24h or ATV 400mg q24h for 14 days. | 19 days |
| D010455 |
| Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D001393 | Azoles |