HIV-1 Infection, Infection, Human Immunodeficiency Virus I
Conditions
Keywords
treatment-experienced, RTV, protease inhibitor, ritonavir, GW640385, HIV-1
Brief summary
This is a two phase study (randomised and non-randomised phase). The randomised phase will initially examine 4 blinded doses of GW640385 boosted with rtv (with continuation of current background therapy) in comparison to an ongoing, open-labeled rtv-boosted protease inhibitor (PI) regimen for 15 days. At the Day 15 visit, all subjects will optimize background therapy. Additionally, subjects receiving the lowest dose of GW640385 will be re-randomised to one of the higher doses and subjects in the control arm will receive a new rtv-boosted PI based on resistance testing at screening. Subjects will remain in the randomized phase on one of these 4 continuing treatment arms for at least 48 weeks. An interim analysis will occur during the randomised phase to select for a dose of GW640385 to evaluate further in Phase III studies. After dose selection subjects will move to the non-randomised phase of the study. In the non-randomised phase subjects who are receiving GW640385 will be assigned to final selected dose for assessment of long term safety, tolerability, pharmacokinetics, and antiviral activity.
Detailed description
A Phase IIB, Randomized, Multicenter, Parallel Group Study to Evaluate the Short-Term Safety, PK and Antiviral Activity of Four Dosing Regimens of GW640385/rtv Therapy Compared to Open-label Current Protease Inhibitor (PI) Therapy in HIV-1, PI-Experienced Adults for 2 wks with Long-Term Evaluation (\>48 wks) of Safety, PK and Antiviral Activity of Selected GW640385/rtv Dosing Regimen(s) vs. a RTV-boosted, PI Containing Regimen
Interventions
DRUGPhysician determined comparator PI + ritonavir
DRUGGW640385 + ritonavir
Sponsors
ViiV Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18+ years of age (or =16 years of age for non-EU countries, according to local requirements). * HIV-1 infected subjects. * Females must be of either non-childbearing potential or have a negative pregnancy test at Screening and agree to use a protocol approved method of contraception. * Plasma HIV-1 RNA (viral load) =1,000 copies/mL at Screening. * Evidence of at least 2 multi-PI resistant mutations at Screening or within 3 months of Screening. * Subjects must have been receiving the same anti-HIV medicines that they are on currently for at least 8 weeks prior to Screening; these anti-HIV medicines will include a single protease inhibitor (PI) in combination with a low dose of ritonavir (i.e., a ritonavir-boosted PI). However, the current PI cannot be tipranavir. * Able to understand and follow protocol requirements, instructions and protocol-stated restrictions. * Be willing and able to provide signed and dated written informed consent prior to study entry.
Exclusion criteria
* Subjects cannot change their anti-HIV medicines between Screening and Day 1 Visit. * Subjects can not be receiving dual ritonavir-boosted PIs, non-nucleoside reverse transcriptase inhibitors (NNRTIs) or Tipranavir at Screening. * Active CDC Class C disease at screening. * Pregnant or breastfeeding women. * Protocol-specified laboratory abnormalities at Screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in laboratory parameters | — |
| Time averaged change in plasma HIV-1 RNA over 16 wks | — |
| Proportion of subjects achieving the target pharmacokinetic (PK) GW640385 drug levels | — |
Secondary
| Measure | Time frame |
|---|---|
| The incidence of adverse events | — |
| Changes in laboratory measurements | — |
| ECG measurements | — |
| HIV viral resistance assessment | — |
| Immunologic measures | — |
| Assessments of HIV viral load changes | — |
| GW640385 and RTV pharmacokinetic measurements | — |
Countries
Australia, Belgium, Canada, France, Germany, Italy, Portugal, Puerto Rico, Romania, United Kingdom, United States
Outcome results
None listed