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Pharmacokinetic Study of Posaconazole Boosted Fosamprenavir (EPOS)

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00817765
First received: December 24, 2008
Last updated: November 27, 2009
Last verified: November 2009

December 24, 2008
November 27, 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. ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00817765 on ClinicalTrials.gov Archive Site
Adverse events (safety) due to concomitant use of fosamprenavir and posaconazole [ Time Frame: period of interaction treatment ] [ Designated as safety issue: Yes ]
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.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: 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
    Interventions:
    • 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)
    Interventions:
    • Drug: Posaconazole
    • Drug: Fosamprenavir
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
24
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
Both
18 Years to 55 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Netherlands
 
NCT00817765
UMCN-AKF 08.03
No
Dr. D.M. Burger, hospital pharmacist, Radboud University Nijmegen Medical Centre
Radboud University
GlaxoSmithKline
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