Pharmacokinetic Study of Posaconazole Boosted Fosamprenavir (EPOS)

November 9, 2020 updated by: Radboud University Medical Center
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Gelderland
      • Nijmegen, Gelderland, Netherlands
        • Radboud University Nijmegen Medical Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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 Names:
  • Telzir / Lexiva
Drug: Ritonavir
Ritonavir 100mg capsule; 1 capsule BID for 10 days
Other Names:
  • 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 Names:
  • Noxafil
Drug: Fosamprenavir
fosamprenavir tablet 700mg; 1 tablet BID for 10 days
Other Names:
  • Telzir / Lexiva

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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.
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

Outcome Measure
Time Frame
Adverse events (safety) due to concomitant use of fosamprenavir and posaconazole
Time Frame: period of interaction treatment
period of interaction treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Collaborators

GlaxoSmithKline

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2009

Primary Completion (ACTUAL)

July 1, 2009

Study Completion (ACTUAL)

October 1, 2009

Study Registration Dates

First Submitted

December 24, 2008

First Submitted That Met QC Criteria

January 5, 2009

First Posted (ESTIMATE)

January 6, 2009

Study Record Updates

Last Update Posted (ACTUAL)

November 12, 2020

Last Update Submitted That Met QC Criteria

November 9, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UMCN-AKF 08.03

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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