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Pharmacokinetic Study of Posaconazole Boosted Fosamprenavir (EPOS)

This study has been completed.
Information provided by:
Radboud University Identifier:
First received: December 24, 2008
Last updated: November 27, 2009
Last verified: November 2009
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 Intervention Phase
HIV Infection
Fungal Infection
Drug: Posaconazole
Drug: Fosamprenavir
Drug: Ritonavir
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacokinetic Study of Posaconazole Boosted Fosamprenavir

Resource links provided by NLM:

Further study details as provided by Radboud University:

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 ]

Estimated Enrollment: 24
Study Start Date: January 2009
Study Completion Date: October 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)
Drug: Posaconazole
Posaconazole oral solution 40mg/mL; 400mg BID treatment for 10 days, including dose escalation
Other Name: Noxafil
Active Comparator: Fosamprenavir ritonavir
Fosamprenavir 700mg / ritonavir 100mg BID for 10 days
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
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)
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

Detailed Description:

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.


Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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
  Contacts and Locations
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Please refer to this study by its identifier: NCT00817765

Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, Netherlands
Sponsors and Collaborators
Radboud University
Principal Investigator: David M Burger, PharmD PhD Radboud University
  More Information

Responsible Party: Dr. D.M. Burger, hospital pharmacist, Radboud University Nijmegen Medical Centre Identifier: NCT00817765     History of Changes
Other Study ID Numbers: UMCN-AKF 08.03
Study First Received: December 24, 2008
Last Updated: November 27, 2009

Keywords provided by Radboud University:
drug-drug interaction

Additional relevant MeSH terms:
HIV Infections
Communicable Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
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 processed this record on May 25, 2017