Pharmacokinetic Study of Posaconazole Boosted Fosamprenavir - Full Text View

Purpose

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.

Condition	Intervention	Phase
HIV Infection Fungal Infection	Drug: Posaconazole Drug: Fosamprenavir Drug: Ritonavir	Phase 1


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Pharmacokinetic Study of Posaconazole Boosted Fosamprenavir

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Ritonavir Posaconazole Fosamprenavir Fosamprenavir sodium Fosamprenavir calcium

U.S. FDA Resources

Further study details as provided by Radboud University:

Primary Outcome Measures:

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. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Adverse events (safety) due to concomitant use of fosamprenavir and posaconazole [ Time Frame: period of interaction treatment ] [ Designated as safety issue: Yes ]


Estimated Enrollment:	24
Study Start Date:	January 2009
Study Completion Date:	October 2009
Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 Name: 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 Name: Telzir / Lexiva Drug: Ritonavir Ritonavir 100mg capsule; 1 capsule BID for 10 days Other Name: 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 Name: Noxafil Drug: Fosamprenavir fosamprenavir tablet 700mg; 1 tablet BID for 10 days Other Name: Telzir / Lexiva

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.

Eligibility


Ages Eligible for Study:	18 Years to 55 Years (Adult)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00817765

Locations


Netherlands
Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, Netherlands

Sponsors and Collaborators

Radboud University

GlaxoSmithKline

Investigators


Principal Investigator:	David M Burger, PharmD PhD	Radboud University

More Information


Responsible Party:	Dr. D.M. Burger, hospital pharmacist, Radboud University Nijmegen Medical Centre
ClinicalTrials.gov Identifier:	NCT00817765 History of Changes
Other Study ID Numbers:	UMCN-AKF 08.03
Study First Received:	December 24, 2008
Last Updated:	November 27, 2009
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:


interaction pharmacokinetics boosting drug-drug interaction safety

Additional relevant MeSH terms:


Infection Communicable Diseases HIV Infections Mycoses Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Ritonavir Fosamprenavir Posaconazole	HIV Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors Antifungal Agents Trypanocidal Agents Antiprotozoal Agents Antiparasitic Agents 14-alpha Demethylase Inhibitors

ClinicalTrials.gov processed this record on September 28, 2016

Pharmacokinetic Study of Posaconazole Boosted Fosamprenavir (EPOS)