Pharmacokinetic Study of Posaconazole Boosted Fosamprenavir (EPOS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00817765
Recruitment Status : Completed
First Posted : January 6, 2009
Last Update Posted : December 1, 2009
Information provided by:
Radboud University

December 24, 2008
January 6, 2009
December 1, 2009
January 2009
July 2009   (Final data collection date for primary outcome measure)
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. ]
Same as current
Complete list of historical versions of study NCT00817765 on Archive Site
Adverse events (safety) due to concomitant use of fosamprenavir and posaconazole [ Time Frame: period of interaction treatment ]
Same as current
Not Provided
Not Provided
Pharmacokinetic Study of Posaconazole Boosted Fosamprenavir
Pharmacokinetic Study of Posaconazole Boosted Fosamprenavir
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.

Phase 1
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • HIV Infection
  • Fungal Infection
  • 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
  • Drug: Ritonavir
    Ritonavir 100mg capsule; 1 capsule BID for 10 days
    Other Name: Norvir
  • 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)
    Intervention: Drug: Posaconazole
  • Active Comparator: Fosamprenavir ritonavir
    Fosamprenavir 700mg / ritonavir 100mg BID for 10 days
    • Drug: Fosamprenavir
    • Drug: Ritonavir
  • 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
    • Drug: Fosamprenavir
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Same as current
October 2009
July 2009   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 55 Years   (Adult)
Contact information is only displayed when the study is recruiting subjects
UMCN-AKF 08.03
Not Provided
Not Provided
Dr. D.M. Burger, hospital pharmacist, Radboud University Nijmegen Medical Centre
Radboud University
Principal Investigator: David M Burger, PharmD PhD Radboud University
Radboud University
November 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP