NCT00765271

Abacavir Pharmacokinetic Study in the Absence/Presence of Darunavir/Ritonavir or Raltegravir in HIV-infected Subjects

A Study Investigating Plasma Abacavir and Its Intracellular Anabolite Carbovir-triphosphate Pharmacokinetics in the Absence and in the Presence of Darunavir/Ritonavir or Raltegravir in HIV-infected Subjects.

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 29 (actual)
• Sponsor: St Stephens Aids Trust · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

The study is being conducted as we have found that many patients with Human Immunodeficiency Disease (HIV) require a combination of different drugs to treat the HIV infection. Before using different combination of drugs, it is important to do studies to see if the drugs will affect the activity of one another. The study aims to help us understand if darunavir/ritonavir or raltegravir have any effects on levels of abacavir in the blood. The purpose of the study is to assess the pharmacokinetics (how a drug is absorbed, distributed and eliminated from your body) of abacavir in the absence and in the presence of darunavir/ritonavir and raltegravir.

Detailed description

Since the co-administration of nucleoside analogues and protease inhibitors, and soon integrase inhibitors, forms an integral part of highly active antiretroviral therapy (HAART) and these combinations may result in unexpected drug interactions (as demonstrated by interactions between protease inhibitors and TFV), it is therefore important to elucidate the impact of ARV co-administration on drug levels. The risk of ABC hypersensitivity (HSR) precludes the study of this agent in healthy volunteers therefore this study will be performed in HIV-infected subjects. Clinical efficacy of drugs is related to their plasma concentrations \[Boffito, 2005\] and it is important to know whether ABC has any impact on the levels of therapeutic agents that may impact on their clinical efficacy. Moreover, it is still unknown whether ABC exposure is altered by the ritonavir-boosted protease inhibitors darunavir or by the new HIV drug raltegravir. Raltegravir will be soon approved for the treatment of HIV in Europe and United States. Pharmacogenetics holds promise in HIV treatment because of the complexity and potential toxicity of multi antiretroviral drug therapies that are prescribed for long periods. Thus far, few candidate genes have been examined for a limited number of allelic variants, but a number of confirmed associations have already emerged. From a public health perspective, as antiretroviral medications become increasingly available to racially and ethnically diverse populations worldwide, understanding the genetic structures of each population may allow us to anticipate the impact of adverse responses, even in groups that were not represented in drug registration trials. The existing literature on pharmacogenetic determinants of antiretroviral drug exposure, drug toxicity, as well as genetic markers associated with the rate of disease progression underline the recent advances which occurred in the past few years. However, it is expected that larger-scale comprehensive genome approaches will profoundly change the landscape of knowledge in the future. Additional studies are needed to assess the implications for long-term responses to antiretroviral agents. For this reason we plan to collect a single blood sample from each participant in our intensive pharmacokinetic studies, such as this one, in order to be able to investigate the association between genetic polymorphisms in drug disposition genes (such as those encoding for cytochrome P450 isoenzymes or transmembrane transporters) and drug exposure. A candidate gene approach will be utilised to examine loci of interest. This procedure will provide potentially important information on genetic influences on plasma drug concentrations and give insight into how to improve the management of HIV-infected patients by individualising therapy. These studies will not be powered for genetic associations but will enable us to build a data base of genotype-phenotype. Prospective genetic studies would need to be planned based on these preliminary data.

Conditions

• HIV

Interventions

Type	Name	Description
DRUG	Abacavir	Group 1 will be instructed to take • Abacavir 600 mg once daily (two 300 mg tablets once daily) as part of regular treatment throughout the whole study Group 2 will be instructed to take • Abacavir 600 mg once daily (two 300 mg tablets once daily) as part of regular treatment throughout the whole study
DRUG	Darunavir/ritonavir	Group 1 will be instructed to take • Three 300mg Darunavir tablets and one 100mg ritonavir tablet once a day for 14 days (on days 2 - 15)
DRUG	Raltegravir	Group 1 will be instructed to take • Two 200mg Raltegravir tablets twice daily for 14 days (on 16 - 29) Group 2 will be instructed to take • Two 200mg Raltegravir tablets twice daily for 14 days (on days 2-15)

Timeline

• Start date: 2008-05-01
• Primary completion: 2008-10-01
• Completion: 2008-10-01
• First posted: 2008-10-02
• Last updated: 2009-11-18

Locations

1 site across 1 country: United Kingdom