Clinical trial NCT00242879: A Dose Ranging Study Of GW640385 Boosted With Ritonavir (Rtv) In Comparison To A RTV-Boosted Protease Inhibitor (PI) In HIV-1 Infected PI-Experienced Adults
Official title: Phase IIB, Randomized, Multicenter, Parallel Group, Study to Evaluate the Safety, Pharmacokinetics and Antiviral Effect of Four Blinded Dosing Regimens of GW640385X/Ritonavir Compared to Open-label Current PI Therapy in HIV-1 Infected, Protease Inhibitor Experienced Adults for 2 Weeks With Long-term Assessment (>48 Weeks) of Safety, Pharmacokinetic and Antiviral Activity of Selected 385/RTV Dosing Regimen(s) vs. a Ritonavir-boosted, Protease Inhibitor Containing Regimen
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Infection, Human Immunodeficiency Virus I
HIV-1 Infection
Keywords: treatment-experienced
RTV
protease inhibitor
ritonavir
GW640385
HIV-1
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
First posted: 2005-10-21
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Time averaged change in plasma HIV-1 RNA over 16 wks
measure: Proportion of subjects achieving the target pharmacokinetic (PK) GW640385 drug levels
measure: Change in laboratory parameters
Secondary outcomes:
measure: Assessments of HIV viral load changes
measure: GW640385 and RTV pharmacokinetic measurements
measure: The incidence of adverse events
measure: Changes in laboratory measurements
measure: ECG measurements
measure: HIV viral resistance assessment
measure: Immunologic measures
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Bakersfield
country: United States
facility: GSK Investigational Site
state: California
city: Fountain Valley
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: Denver
country: United States
facility: GSK Investigational Site
state: Colorado
city: Denver
country: United States
facility: GSK Investigational Site
state: Colorado
city: Norwalk
country: United States
facility: GSK Investigational Site
state: Connecticut
city: Washington, D.C.
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Washington, D.C.
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Bradenton
country: United States
facility: GSK Investigational Site
state: Florida
city: Fort Lauderdale
country: United States
facility: GSK Investigational Site
state: Florida
city: Fort Lauderdale
country: United States
facility: GSK Investigational Site
state: Florida
city: Fort Lauderdale
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: Louisville
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Newark
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Rochester
country: United States
facility: GSK Investigational Site
state: New York
city: Greenville
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Hampton
country: United States
facility: GSK Investigational Site
state: Virginia
city: Darlinghurst
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Liverpool
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: South Yarra
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Vancouver
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Sainte-Foy
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Caen
country: France
facility: GSK Investigational Site
city: La Roche Sur Yon cedex 9
country: France
facility: GSK Investigational Site
city: Lyon Cedex 02
country: France
facility: GSK Investigational Site
city: Lyon Cedex 03
country: France
facility: GSK Investigational Site
city: Nantes
country: France
facility: GSK Investigational Site
city: Paris Cedex 10
country: France
facility: GSK Investigational Site
city: Paris Cedex 12
country: France
facility: GSK Investigational Site
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Frankfurt
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Bonn
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Ferrara
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Rimini
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Pavia
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Torino
country: Italy
facility: GSK Investigational Site
state: Piemonte
city: Bari
country: Italy
facility: GSK Investigational Site
state: Puglia
city: Bagno a Ripoli (FI)
country: Italy
facility: GSK Investigational Site
state: Toscana
city: Cascais
country: Portugal
facility: GSK Investigational Site
city: Lisboa
country: Portugal
facility: GSK Investigational Site
city: Ponce
country: Puerto Rico
facility: GSK Investigational Site
city: San Juan
country: Puerto Rico
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Constanta
country: Romania
facility: GSK Investigational Site
city: Iasi
country: Romania
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials, MD
role: STUDY_DIRECTOR
References: