Pharmacokinetic Study of Posaconazole Boosted Fosamprenavir

NCT00817765 | Completed Phase 1

• 1 other identifier: UMCN-AKF 08.03
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV Infection; Fungal Infection

Keywords

interaction; pharmacokinetics; boosting; drug-drug interaction; safety

Outcome Measures

Primary Outcomes (1)

• Plasma concentrations of amprenavir and posaconazole

  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

  period of interaction treatment

Study Arms (3)

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

Fosamprenavir ritonavir

ACTIVE COMPARATOR

Fosamprenavir 700mg / ritonavir 100mg BID for 10 days

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)

Drug: Posaconazole; Drug: Fosamprenavir

Interventions

Posaconazole DRUG

Posaconazole oral solution 40mg/mL; 400mg BID treatment for 10 days, including dose escalation

Also known as: Noxafil

Fosamprenavir posaconazole; Posaconazole alone

Fosamprenavir DRUG

fosamprenavir tablet 700mg; 1 tablet BID for 10 days

Also known as: Telzir / Lexiva

Fosamprenavir posaconazole; Fosamprenavir ritonavir

Ritonavir DRUG

Ritonavir 100mg capsule; 1 capsule BID for 10 days

Also known as: Norvir

Fosamprenavir ritonavir

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Radboud University Medical Center: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Radboud University Nijmegen Medical Centre

Nijmegen, Gelderland, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 20667889 RESULT

MeSH Terms

Conditions

HIV Infections; Mycoses

Interventions

posaconazole; fosamprenavir; Ritonavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• David M Burger, PharmD PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 24, 2008
• First Posted: January 6, 2009
• Study Start: January 1, 2009
• Primary Completion: July 1, 2009
• Study Completion: October 1, 2009
• Last Updated: November 12, 2020

Record last verified: 2020-11

Locations

NL (1)