Abacavir Pharmacokinetic Study in the Absence/Presence of Darunavir/Ritonavir or Raltegravir in HIV-infected Subjects

NCT00765271 | Completed Phase 1

• 2 other identifiers: SSAT026EudraCT No: 2007-005965-37
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

The study is being conducted as we have found that many patients with Human Immunodeficiency Disease (HIV) require a combination of different drugs to treat the HIV infection. Before using different combination of drugs, it is important to do studies to see if the drugs will affect the activity of one another. The study aims to help us understand if darunavir/ritonavir or raltegravir have any effects on levels of abacavir in the blood. The purpose of the study is to assess the pharmacokinetics (how a drug is absorbed, distributed and eliminated from your body) of abacavir in the absence and in the presence of darunavir/ritonavir and raltegravir.

Conditions

HIV

Outcome Measures

Primary Outcomes (1)

• Steady state plasma concentrations of abacavir and intracellular concentrations of its active anabolite carbovir-TP following the administration of abacavir 600 mg once daily, in the absence and in the presence of darunavir/ritonavir or raltegravir

  30 days

Secondary Outcomes (1)

• Plasma pharmacokinetics of darunavir/ritonavir and raltegravir in the presence of abacavir in HIV-infected subjects Safety and tolerability of abacavir in the presence of darunavir/ritonavir or raltegravir in HIV-infected subjects

  30 days

Study Arms (2)

Group 2

ACTIVE COMPARATOR

Abacavir 600 mg (2 x 300mg tablet) once daily throughout the study (days 1- 30) Raltegravir 400 mg (2 x 200mg tablets) twice daily from days 2 to 15 Darunavir/ritonavir 900 (3 x 300mg tablets)/100 (1 x 100mg capsule) mg once daily from day 16 to day 29)

Drug: Abacavir; Drug: Raltegravir

Group 1

ACTIVE COMPARATOR

Abacavir 600 mg (2 x 300mg tablet) once daily throughout the study (days 1- 30) Darunavir/ritonavir 900 (3 x 300mg tablets)/100 (1 x 100mg capsule) mg once daily from day 2 to day 15) Raltegravir 400 mg (2 x 200mg tablets) twice daily from day 16 to 29

Drug: Abacavir; Drug: Darunavir/ritonavir; Drug: Raltegravir

Interventions

Abacavir DRUG

Group 1 will be instructed to take • Abacavir 600 mg once daily (two 300 mg tablets once daily) as part of regular treatment throughout the whole study Group 2 will be instructed to take • Abacavir 600 mg once daily (two 300 mg tablets once daily) as part of regular treatment throughout the whole study

Also known as: Ziagen®, Trizivir®, Kivexa®.

Group 1; Group 2

Darunavir/ritonavir DRUG

Group 1 will be instructed to take • Three 300mg Darunavir tablets and one 100mg ritonavir tablet once a day for 14 days (on days 2 - 15)

Group 1

Raltegravir DRUG

Group 1 will be instructed to take • Two 200mg Raltegravir tablets twice daily for 14 days (on 16 - 29) Group 2 will be instructed to take • Two 200mg Raltegravir tablets twice daily for 14 days (on days 2-15)

Group 1; Group 2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The ability to understand and sign a written informed consent form, prior to participation in any screening procedure and must be willing to comply with all study requirements.
• Male or non-pregnant, non-lactating females.
• Between 18 to 65 years, inclusive.
• Documented HIV-1 infection and plasma HIV RNA at screening visit below 400 copies/mL. (Note retesting of screening viral load is allowed).
• CD4 count \> 100 at screening (Note retesting of screening CD4 count is allowed).
• Receiving an abacavir-containing regimen which does not include tenofovir, a protease inhibitor, a non-nucleoside reverse transcriptase inhibitor or a fusion inhibitor at screening.
• Agrees not to change regimen from baseline until end of the treatment period unless this is medically indicated as decided by the treating physician.

You may not qualify if:

• Any serious or active medical or psychiatric illness which, in the opinion of the investigator, would interfere with subject treatment, assessment, or compliance with the protocol. This would include any active clinically significant renal, cardiac, hepatic, pulmonary, vascular, metabolic disorders or malignancy.
• Have a body mass index (BMI) \>30
• Presence of any current active AIDS defining illness (Category C conditions according to the CDC Classification System for HIV Infection 1993) with the following exceptions:
• Stable cutaneous Kaposi's Sarcoma
• Clinically relevant alcohol or drug use (positive urine drug screen) or history of alcohol or drug use considered by the Investigator to be sufficient to hinder compliance with treatment, follow-up procedures or evaluation of adverse events. Smoking is permitted, but tobacco intake should remain consistent throughout the study.
• Concurrent use of non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors, fusion inhibitors or tenofovir.
• \. The use of disallowed concomitant therapy (See Concomitant Medication and treatment, section 5.2).
• \. Females of childbearing potential without the use of effective non-hormonal birth control methods or not willing to continue practicing these birth control methods for at least 14 days after the end of the treatment period.
• \. Previous allergy to any of the constituents of the pharmaceuticals administered in this trial.
• \. Subjects with clinical or laboratory evidence of significantly decreased hepatic or renal function (as determined by the principal investigator).

Sponsors & Collaborators

• St Stephens Aids Trust: lead

Study Sites (1)

Chelsea and Westminster Hospital

London, London, SW10 9TH, United Kingdom

Location

MeSH Terms

Interventions

abacavir; abacavir, lamivudine, and zidovudine drug combination; abacavir, lamivudine drug combination; Darunavir; Ritonavir; Raltegravir Potassium

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles; Pyrrolidinones; Pyrrolidines

Study Officials

• Marta Boffito

  St Stephen's AIDS Trust

  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: October 1, 2008
• First Posted: October 2, 2008
• Study Start: May 1, 2008
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: November 18, 2009

Record last verified: 2009-11

Locations

GB (1)