Back to resultsPharmacokinetic Study of Posaconazole Boosted Fosamprenavir (EPOS)
Primary Purpose
HIV Infection, Fungal Infection
Status
Completed
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
Posaconazole
Fosamprenavir
Ritonavir
Sponsored by
About this trial
This is an interventional treatment trial for HIV Infection focused on measuring interaction, pharmacokinetics, boosting, drug-drug interaction, safety
Eligibility Criteria
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
Sites / Locations
- Radboud University Nijmegen Medical Centre
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Experimental
Arm Label
Posaconazole alone
Fosamprenavir ritonavir
Fosamprenavir posaconazole
Arm Description
400mg posaconazole BID for 10 days (start on day 1 with 200mg QD, day 2 200mg BID; from day 3 onwards 400mg BID)
Fosamprenavir 700mg / ritonavir 100mg BID for 10 days
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)
Outcomes
Primary Outcome Measures
Plasma concentrations of amprenavir and posaconazole
Secondary Outcome Measures
Adverse events (safety) due to concomitant use of fosamprenavir and posaconazole
Full Information
NCT ID
NCT00817765
First Posted
December 24, 2008
Last Updated
November 9, 2020
Sponsor
Radboud University Medical Center
Collaborators
GlaxoSmithKline
1. Study Identification
Unique Protocol Identification Number
NCT00817765
Brief Title
Pharmacokinetic Study of Posaconazole Boosted Fosamprenavir
Acronym
EPOS
Official Title
Pharmacokinetic Study of Posaconazole Boosted Fosamprenavir
Study Type
Interventional
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
July 2009 (Actual)
Study Completion Date
October 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Radboud University Medical Center
Collaborators
GlaxoSmithKline
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infection, Fungal Infection
Keywords
interaction, pharmacokinetics, boosting, drug-drug interaction, safety
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
24 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Posaconazole alone
Arm Type
Active Comparator
Arm Description
400mg posaconazole BID for 10 days (start on day 1 with 200mg QD, day 2 200mg BID; from day 3 onwards 400mg BID)
Arm Title
Fosamprenavir ritonavir
Arm Type
Active Comparator
Arm Description
Fosamprenavir 700mg / ritonavir 100mg BID for 10 days
Arm Title
Fosamprenavir posaconazole
Arm Type
Experimental
Arm 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)
Intervention Type
Drug
Intervention Name(s)
Posaconazole
Other Intervention Name(s)
Noxafil
Intervention Description
Posaconazole oral solution 40mg/mL; 400mg BID treatment for 10 days, including dose escalation
Intervention Type
Drug
Intervention Name(s)
Fosamprenavir
Other Intervention Name(s)
Telzir / Lexiva
Intervention Description
fosamprenavir tablet 700mg; 1 tablet BID for 10 days
Intervention Type
Drug
Intervention Name(s)
Ritonavir
Other Intervention Name(s)
Norvir
Intervention Description
Ritonavir 100mg capsule; 1 capsule BID for 10 days
Primary Outcome Measure Information:
Title
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.
Secondary Outcome Measure Information:
Title
Adverse events (safety) due to concomitant use of fosamprenavir and posaconazole
Time Frame
period of interaction treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David M Burger, PharmD PhD
Organizational Affiliation
Radboud University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Radboud University Nijmegen Medical Centre
City
Nijmegen
State/Province
Gelderland
Country
Netherlands
12. IPD Sharing Statement
Citations:
PubMed Identifier
20667889
Citation
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.
Results Reference
result
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Pharmacokinetic Study of Posaconazole Boosted Fosamprenavir
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