Pharmacokinetic Study of Posaconazole Boosted Fosamprenavir (EPOS)
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| ClinicalTrials.gov Identifier: NCT00817765 |
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Recruitment Status :
Completed
First Posted : January 6, 2009
Last Update Posted : December 1, 2009
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Sponsor:
Radboud University
Collaborator:
GlaxoSmithKline
Information provided by:
Radboud University
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Brief Summary:
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| HIV Infection Fungal Infection | Drug: Posaconazole Drug: Fosamprenavir Drug: Ritonavir | Phase 1 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 24 participants |
| Allocation: | Randomized |
| Intervention Model: | Crossover Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Pharmacokinetic Study of Posaconazole Boosted Fosamprenavir |
| Study Start Date : | January 2009 |
| Actual Primary Completion Date : | July 2009 |
| Actual Study Completion Date : | October 2009 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Posaconazole alone
400mg posaconazole BID for 10 days (start on day 1 with 200mg QD, day 2 200mg BID; from day 3 onwards 400mg BID)
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Drug: Posaconazole
Posaconazole oral solution 40mg/mL; 400mg BID treatment for 10 days, including dose escalation
Other Name: Noxafil |
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Active Comparator: Fosamprenavir ritonavir
Fosamprenavir 700mg / ritonavir 100mg BID for 10 days
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Drug: Fosamprenavir
fosamprenavir tablet 700mg; 1 tablet BID for 10 days
Other Name: Telzir / Lexiva Drug: Ritonavir Ritonavir 100mg capsule; 1 capsule BID for 10 days
Other Name: Norvir |
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Experimental: Fosamprenavir posaconazole
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)
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Drug: Posaconazole
Posaconazole oral solution 40mg/mL; 400mg BID treatment for 10 days, including dose escalation
Other Name: Noxafil Drug: Fosamprenavir fosamprenavir tablet 700mg; 1 tablet BID for 10 days
Other Name: Telzir / Lexiva |
Primary Outcome Measures :
- Plasma concentrations of amprenavir and posaconazole [ Time Frame: 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. ]
Secondary Outcome Measures :
- Adverse events (safety) due to concomitant use of fosamprenavir and posaconazole [ Time Frame: period of interaction treatment ]
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| Ages Eligible for Study: | 18 Years to 55 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
Criteria
Inclusion Criteria:
- Subject is at least 18 and not older than 55 years of age on the day of the first dosing.
- Subject does not smoke more than 10 cigarettes, 2 cigars, or 2 pipes per day for at least 3 months prior to the first dosing.
- Subject has a Quetelet Index (Body Mass Index) of 18 to 30 kg/m2, extremes included.
- Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
- Subject is in good age-appropriate health condition as established by medical history, physical examination, electrocardiography, results of biochemistry, haematology and urinalysis testing within 4 weeks prior to the first dose.
- Subject has a normal blood pressure and pulse rate, according to the Investigator's judgement.
Exclusion Criteria:
- Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
- Positive HIV test.
- Positive hepatitis B or C test.
- Pregnant female (as confirmed by an HCG test performed less than 4 weeks before the first dose) or breast-feeding female.
- Therapy with any drug (for two weeks preceding dosing), except for paracetamol.
- Subjects with an ECG with QTc interval greater than 450 ms for men, and greater than 470 ms for women at screening.
- Relevant history or presence of pulmonary disorders (especially COPD), cardiovascular disorders, neurological disorders (especially seizures and migraine), gastro-intestinal disorders, renal and hepatic disorders, hormonal disorders (especially diabetes mellitus), coagulation disorders.
- Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
- History of or current abuse of drugs, alcohol or solvents.
- Inability to understand the nature and extent of the trial and the procedures required.
- Participation in a drug trial within 60 days prior to the first dose.
- Donation of blood within 60 days prior to the first dose.
- Febrile illness within 3 days before the first dose
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00817765
Locations
| Netherlands | |
| Radboud University Nijmegen Medical Centre | |
| Nijmegen, Gelderland, Netherlands | |
Sponsors and Collaborators
Radboud University
GlaxoSmithKline
Investigators
| Principal Investigator: | David M Burger, PharmD PhD | Radboud University |
| Responsible Party: | Dr. D.M. Burger, hospital pharmacist, Radboud University Nijmegen Medical Centre |
| ClinicalTrials.gov Identifier: | NCT00817765 History of Changes |
| Other Study ID Numbers: |
UMCN-AKF 08.03 |
| First Posted: | January 6, 2009 Key Record Dates |
| Last Update Posted: | December 1, 2009 |
| Last Verified: | November 2009 |
Keywords provided by Radboud University:
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interaction pharmacokinetics boosting drug-drug interaction safety |
Additional relevant MeSH terms:
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Infection Communicable Diseases HIV Infections Mycoses Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Ritonavir Fosamprenavir Posaconazole |
HIV Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors Antifungal Agents Trypanocidal Agents Antiprotozoal Agents Antiparasitic Agents 14-alpha Demethylase Inhibitors |