Pharmacokinetic Study of Posaconazole Boosted Fosamprenavir (EPOS)

Radboud University Medical Center

Status and phase: Completed; Phase 1

Conditions: Fungal Infection; HIV Infection

Treatments: Drug: Ritonavir; Drug: Fosamprenavir; Drug: Posaconazole

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00817765

UMCN-AKF 08.03

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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24 participants in 3 patient groups

Posaconazole alone

Active Comparator group

Description:

400mg posaconazole BID for 10 days (start on day 1 with 200mg QD, day 2 200mg BID; from day 3 onwards 400mg BID)

Treatment:

Drug: Posaconazole

Fosamprenavir ritonavir

Active Comparator group

Description:

Fosamprenavir 700mg / ritonavir 100mg BID for 10 days

Treatment:

Drug: Ritonavir

Drug: Fosamprenavir

Fosamprenavir posaconazole

Experimental group

Description:

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)

Treatment:

Drug: Posaconazole

Drug: Fosamprenavir