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| Name | Class |
|---|---|
| GlaxoSmithKline | INDUSTRY |
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The purpose of this study is to determine the influence of posaconazole on unboosted fosamprenavir pharmacokinetics, and vice versa, in healthy volunteers.A second objective is to determine the safety of combined use of fosamprenavir with posaconazole in healthy volunteers.
Infections with fungi and yeast frequently occur in patients infected with the human immunodeficiency virus type 1 (HIV-1).
Fosamprenavir is a PI that is used to treat HIV-infection in combination with ritonavir. Once hydrolyzed to amprenavir, this substance is a substrate for CYP3A4. Ritonavir is an extremely potent inhibitor of CYP3A4 and serves as a booster of the pharmacokinetics of amprenavir. Posaconazole is a very potent CYP3A4 inhibitor and therefore might enhance amprenavir pharmacokinetics in a similar way as ritonavir.
The current study is designed to test this hypothesis. When there is an indication for antifungal therapy in an HIV-infected patient, temporal replacement of ritonavir by posaconazole would be an attractive option for combined treatment of HIV and fungal infection.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Posaconazole alone | Active Comparator | 400mg posaconazole BID for 10 days (start on day 1 with 200mg QD, day 2 200mg BID; from day 3 onwards 400mg BID) |
|
| Fosamprenavir ritonavir | Active Comparator | Fosamprenavir 700mg / ritonavir 100mg BID for 10 days |
|
| Fosamprenavir posaconazole | Experimental | Fosamprenavir 700mg / posaconazole 400mg BID for 10 days (start on day 1 with 200mg QD, day 2 200mg BID; from day 3 onwards 400mg BID) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Posaconazole | Drug | Posaconazole oral solution 40mg/mL; 400mg BID treatment for 10 days, including dose escalation |
|
| Measure | Description | Time Frame |
|---|---|---|
| Plasma concentrations of amprenavir and posaconazole | predose and at 1, 2, 3, 4, 5, 6, 7, 8, 10 and 12 hours after dosing on Study Days 10, 38 and 66. Predose on study days 1, 3, 5, 8, 29, 31, 33, 36, 57, 59, 61, and 64. |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse events (safety) due to concomitant use of fosamprenavir and posaconazole | period of interaction treatment |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David M Burger, PharmD PhD | Radboud University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Radboud University Nijmegen Medical Centre | Nijmegen | Gelderland | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20667889 | Result | Bruggemann RJ, van Luin M, Colbers EP, van den Dungen MW, Pharo C, Schouwenberg BJ, Burger DM. Effect of posaconazole on the pharmacokinetics of fosamprenavir and vice versa in healthy volunteers. J Antimicrob Chemother. 2010 Oct;65(10):2188-94. doi: 10.1093/jac/dkq280. Epub 2010 Jul 28. |
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| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D009181 | Mycoses |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
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| ID | Term |
|---|---|
| C101425 | posaconazole |
| C426859 | fosamprenavir |
| D019438 | Ritonavir |
| ID | Term |
|---|---|
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D001393 | Azoles |
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|
| Fosamprenavir | Drug | fosamprenavir tablet 700mg; 1 tablet BID for 10 days |
|
|
| Ritonavir | Drug | Ritonavir 100mg capsule; 1 capsule BID for 10 days |
|
|
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D001423 | Bacterial Infections and Mycoses |
| D006573 |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |