Pharmacokinetic Study of Posaconazole Boosted Fosamprenavir - Full Text View

Sponsors and Collaborators:	Radboud University GlaxoSmithKline
Information provided by:	Radboud University
ClinicalTrials.gov Identifier:	NCT00817765

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 I

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Crossover Assignment, Pharmacokinetics Study
Official Title:	Pharmacokinetic Study of Posaconazole Boosted Fosamprenavir

Resource links provided by NLM:

MedlinePlus related topics: AIDS Fungal Infections

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

Arms	Assigned Interventions
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)	Drug: Posaconazole Posaconazole oral solution 40mg/mL; 400mg BID treatment for 10 days, including dose escalation
Fosamprenavir ritonavir: Active Comparator Fosamprenavir 700mg / ritonavir 100mg BID for 10 days	Drug: Fosamprenavir fosamprenavir tablet 700mg; 1 tablet BID for 10 days Drug: Ritonavir Ritonavir 100mg capsule; 1 capsule BID for 10 days
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)	Drug: Posaconazole Posaconazole oral solution 40mg/mL; 400mg BID treatment for 10 days, including dose escalation Drug: Fosamprenavir fosamprenavir tablet 700mg; 1 tablet BID for 10 days

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
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

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

Locations

Netherlands, Gelderland
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

No publications provided

Responsible Party:	Radboud University Nijmegen Medical Centre ( Dr. D.M. Burger, hospital pharmacist )
Study ID Numbers:	UMCN-AKF 08.03
Study First Received:	December 24, 2008
Last Updated:	July 21, 2009
ClinicalTrials.gov Identifier:	NCT00817765 History of Changes
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:

interaction
pharmacokinetics
boosting
drug-drug interaction
safety

Study placed in the following topic categories:

Anti-Infective Agents
Sexually Transmitted Diseases, Viral
HIV Protease Inhibitors
Anti-HIV Agents
Acquired Immunodeficiency Syndrome
Antiviral Agents
Immunologic Deficiency Syndromes
Protease Inhibitors
Virus Diseases
Anti-Bacterial Agents

Mycoses
Anti-Retroviral Agents
Fosamprenavir
HIV Infections
Ritonavir
Antifungal Agents
Sexually Transmitted Diseases
Posaconazole
Retroviridae Infections

Additional relevant MeSH terms:

Trypanocidal Agents
Anti-Infective Agents
Communicable Diseases
Antiprotozoal Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Infection
Mycoses
Antiparasitic Agents
Anti-Retroviral Agents
Antifungal Agents
Therapeutic Uses
Antibiotics, Antifungal
Posaconazole

Retroviridae Infections
RNA Virus Infections
HIV Protease Inhibitors
Anti-HIV Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Protease Inhibitors
Virus Diseases
Fosamprenavir
HIV Infections
Ritonavir

ClinicalTrials.gov processed this record on September 02, 2009