HIV InfectionPhase 1EPOSNCT00817765
Pharmacokinetic Study of Posaconazole Boosted Fosamprenavir
A Phase 1 study testing Posaconazole, Fosamprenavir and Ritonavir in people with HIV Infection and Fungal Infection, run by Radboud University Medical Center at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV Infection, Fungal Infection
- What is being tested?
- Posaconazole, Fosamprenavir and Ritonavir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteNetherlands
- Study dates
- Jan 2009to Oct 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 13Show fewer
- 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 locations and contacts
1 site in 1 country.
Netherlands1 site
Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland
About this study
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.
Read the 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.
- Conditions
- HIV Infection, Fungal Infection
- Being tested
- Posaconazole, Fosamprenavir, Ritonavir
- Keywords
- interaction, pharmacokinetics, boosting, drug-drug interaction, safety
- Medical subject headings
- HIV Infections, Mycoses
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PosaconazoleDrug
Also called Noxafil
Posaconazole oral solution 40mg/mL; 400mg BID treatment for 10 days, including dose escalation
FosamprenavirDrug
Also called Telzir / Lexiva
fosamprenavir tablet 700mg; 1 tablet BID for 10 days
RitonavirDrug
Also called Norvir
Ritonavir 100mg capsule; 1 capsule BID for 10 days
| Study group | Role | What they receive |
|---|---|---|
| Posaconazole alone | Active comparator | 400mg posaconazole BID for 10 days (start on day 1 with 200mg QD, day 2 200mg BID; from day 3 onwards 400mg BID) Receives: Drug: Posaconazole |
| Fosamprenavir ritonavir | Active comparator | Fosamprenavir 700mg / ritonavir 100mg BID for 10 days Receives: Drug: Fosamprenavir; Drug: Ritonavir |
| Fosamprenavir posaconazole | Experimental | 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) Receives: Drug: Posaconazole; Drug: Fosamprenavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma concentrations of amprenavir and posaconazole
Measured: 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 outcomes (1)
Adverse events (safety) due to concomitant use of fosamprenavir and posaconazole
Measured: period of interaction treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2009 (estimated)
- Study startJan 2009
- Primary completionJul 2009
- Study completionOct 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Investigators
- David M Burger, PharmD PhD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00817765
- Sponsor's protocol ID
- UMCN-AKF 08.03
- Acronym
- EPOS
- Status last verified
- Nov 2020
- First submitted
- 24 Dec 2008
- Last updated
- 12 Nov 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 20667889
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetic Study of Posaconazole Boosted Fosamprenavir
- ClinicalTrials.gov ID
- NCT00817765
- Acronym / sponsor ID
- EPOS / UMCN-AKF 08.03
- Conditions
- HIV Infection, Fungal Infection
- Keywords
- interaction, pharmacokinetics, boosting, drug-drug interaction, safety
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- Jan 2009
- Primary completion
- Jul 2009 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 6 Jan 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Posaconazole alone | Active comparator | Drug: Posaconazole400mg posaconazole BID for 10 days (start on day 1 with 200mg QD, day 2 200mg BID; from day 3 onwards 400mg BID) |
| Fosamprenavir ritonavir | Active comparator | Drug: Fosamprenavir, Drug: RitonavirFosamprenavir 700mg / ritonavir 100mg BID for 10 days |
| Fosamprenavir posaconazole | Experimental | Drug: Posaconazole, Drug: FosamprenavirFosamprenavir 700mg / posaconazole 400mg BID for 10 days (start on day 1 with 200mg QD, day 2 200mg BID; from day 3 onwards 400mg BID) |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PosaconazoleAlso: NoxafilPosaconazole oral solution 40mg/mL; 400mg BID treatment for 10 days, including dose escalation | Drug | Fosamprenavir posaconazole, Posaconazole alone |
| FosamprenavirAlso: Telzir / Lexivafosamprenavir tablet 700mg; 1 tablet BID for 10 days | Drug | Fosamprenavir posaconazole, Fosamprenavir ritonavir |
| RitonavirAlso: NorvirRitonavir 100mg capsule; 1 capsule BID for 10 days | Drug | Fosamprenavir ritonavir |
Primary outcome
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.
1 secondary outcome
Adverse events (safety) due to concomitant use of fosamprenavir and posaconazole
Time frame: period of interaction treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2020.
- Results publication: PubMed 20667889Bruggemann 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.
Related trials for HIV Infection
Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Recruiting
Evaluating the Impact of Using the B-OK Bottles for HIV and ART Literacy in South Africa
HIV, HIV Treatment
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David M Burger, PharmD PhD principal investigator
Radboud University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Posaconazole, Fosamprenavir and Ritonavir in people with HIV Infection and Fungal Infection, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00817765, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Nov 2020.