Pharmacokinetic Study of Posaconazole Boosted Fosamprenavir

NCT ID: NCT00817765

Last Updated: 2020-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-01-31

Study Completion Date

2009-10-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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HIV Infection Fungal Infection

Keywords

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interaction pharmacokinetics boosting drug-drug interaction safety

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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)

Group Type ACTIVE_COMPARATOR

Posaconazole

Intervention Type DRUG

Posaconazole oral solution 40mg/mL; 400mg BID treatment for 10 days, including dose escalation

Fosamprenavir ritonavir

Fosamprenavir 700mg / ritonavir 100mg BID for 10 days

Group Type ACTIVE_COMPARATOR

Fosamprenavir

Intervention Type DRUG

fosamprenavir tablet 700mg; 1 tablet BID for 10 days

Ritonavir

Intervention Type DRUG

Ritonavir 100mg capsule; 1 capsule BID for 10 days

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)

Group Type EXPERIMENTAL

Posaconazole

Intervention Type DRUG

Posaconazole oral solution 40mg/mL; 400mg BID treatment for 10 days, including dose escalation

Fosamprenavir

Intervention Type DRUG

fosamprenavir tablet 700mg; 1 tablet BID for 10 days

Interventions

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Posaconazole

Posaconazole oral solution 40mg/mL; 400mg BID treatment for 10 days, including dose escalation

Intervention Type DRUG

Fosamprenavir

fosamprenavir tablet 700mg; 1 tablet BID for 10 days

Intervention Type DRUG

Ritonavir

Ritonavir 100mg capsule; 1 capsule BID for 10 days

Intervention Type DRUG

Other Intervention Names

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Noxafil Telzir / Lexiva Norvir

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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GlaxoSmithKline

INDUSTRY

Sponsor Role collaborator

Radboud University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Radboud University Nijmegen Medical Centre

Principal Investigators

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David M Burger, PharmD PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

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Radboud University Nijmegen Medical Centre

Nijmegen, Gelderland, Netherlands

Site Status

Countries

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Netherlands

References

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Bruggemann RJ, van Luin M, Colbers EP, van den Dungen MW, Pharo C, Schouwenberg BJ, Burger DM. Effect of posaconazole on the pharmacokinetics of fosamprenavir and vice versa in healthy volunteers. J Antimicrob Chemother. 2010 Oct;65(10):2188-94. doi: 10.1093/jac/dkq280. Epub 2010 Jul 28.

Reference Type RESULT
PMID: 20667889 (View on PubMed)

Other Identifiers

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UMCN-AKF 08.03

Identifier Type: -

Identifier Source: org_study_id