An open-label, two-period, crossover, pharmacokinetic study of abacavir and its intracellular anabolite carbovir triphosphate following once-daily and twice-daily administration of abacavir in HIV-infected subjects. - CAL102120

Active, not recruiting

• Conditions: HIV-infection

• Registration Number: EUCTR2004-000754-24-GB
• Lead Sponsor: GlaxoSmithKline R&D UK Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-06-22
• Last Update Posted: 15 July 2013

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

•Healthy adult male or female aged 18-65 years. Females should be of non-childbearing potential or with a negative pregnancy test at screening and agrees to use a form of contraception as detailed in the protocol.
•Able and willing to give written informed consent to participate in the study.
•Documented HIV-1 infection (documented by historical data or current validated assay).
•Undetectable viral load, as determined by an ultra-sensitive assay (<400 copies/mL) at screening.
•Currently on an ABC-containing regimen for at least 8 weeks. A stable regimen of other approved antiretroviral agents (except for tenofovir) is permitted. However, other than switching from ABC BID to QD or vice versa, as per this protocol, there should be no plans to change any component of the antiretroviral regimen until study completion.
•CD4+ cell count > or =250 cells/mm3 at screening.
•Willingness to temporarily switch ABC schedule from BID to QD, or vice versa, for 11 days.
•Weigh between 40-100kg, inclusive and have a Body Mass Index within 19 to 29kg/m2 inclusive.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

•As a result of the medical interview, physical examination or screening investigations, the physician responsible considers the subject unsuitable for the study.
•Subjects who have been on an ABC-containing regimen for less than 8 weeks.
•Subjects that have missed any scheduled doses of ABC during the 3 days prior to the start of the study (Day –3 to –1 inclusive).
•Subjects who are receiving tenofovir.
•Previous study participation in other experimental drug trial(s) within 30 days before the screening phase of the study.
•Subjects who currently regularly take drugs-of-abuse, with the exception of cannabinoids.
•Subjects who cannot refrain from taking herbal remedies during the course of the study (from screening until discharge on Day 12).
• Subjects who regularly consume more than an average of 4 units of alcohol per day (1 unit is defined as 83mL of a 12% strength beverage).
•Subjects with any condition which, in the opinion of the investigator, might interfere with the absorption, distribution, metabolism or excretion of the drug including, but not limited to, diabetes mellitus, hepatic impairment, renal impairment, hyperthyroidism, malabsorption syndrome.
•Poor general health preventing fasting or blood sampling, or any acute illness within seven days prior to dosing that would, in the judgement of the investigator, interfere with participation in the study;
•Subjects who are not able to discontinue use of hydroxyurea, mycophenolate or ribavirin for 14 days prior to entering the study until discharge from the study.
•Liver function tests (AST, ALT, LDH and Alkaline Phosphatase) greater than 3x the upper limit of normal. Bilirubin greater than 2x the upper limit of normal. Liver function tests and/or bilirubin above the upper limits of normal but below the exclusion criteria at screening should be stable or declining at Day –1 and should not represent a new clinical condition for the subject.
•Haemoglobin less than 12g/dL or platelet count less than 50,000/microl.
•An unwillingness of a male subject to abstain from sexual intercourse with women of childbearing potential or an unwillingness to use a condom in addition to having their female partner use another form of contraception if engaging in sexual intercourse with a woman who could become pregnant from the first dose of study medication until the follow-up visit.
•The subject is pregnant or nursing an infant.
•History of symptoms consistent with a hypersensitivity reaction to ABC (i.e., fever, rash, malaise or fatigue, gastrointestinal symptoms such as nausea, vomiting, diarrhoea, or abdominal pain and respiratory symptoms such as dyspnoea, sore throat, or cough) that are deemed related to the administration of ABC by the investigator.
•Positive HCV Antibody or HepBsAg (Hepatitis B surface antigen) test at screening.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the PK of intracellular carbovir triphosphate (CBV-TP) at steady state following administration of 600 mg QD and 300 mg BID ABC-containing regimens in HIV-infected adult subjects.;Secondary Objective: To assess the PK of plasma concentrations of ABC, and its relationship to intracellular CBV-TP, at steady state following administration of ABC 600mg QD and 300mg BID ABC-containing regimens in HIV-infected subjects.<br><br>To assess the safety and tolerability of dosing with ABC 300mg BID and 600mg QD.<br><br>To assess potential gender effects of the pharmacokinetics of ABC after administration of 600mg QD and 300mg BID ABC-containing regimens in HIV-infected male and female subjects.<br>;Primary end point(s): PK parameters for intracellular CBV-TP: AUC(0 24), Cmax , C~, Cavg after administration of ABC 600 mg QD and ABC 300 mg BID.