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

HIV-1 Infection Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00242879
• Other study ID #: HPR20001
• Status: Terminated
• Phase: Phase 2
• First received: October 19, 2005
• Last updated: May 25, 2017
• Start date: August 2005
• Est. completion date: June 2007

Study information

• Verified date: May 2017
• Source: ViiV Healthcare
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 130
• Est. completion date: June 2007
• Est. primary completion date: June 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Communicable Diseases
• HIV Infections
• HIV-1 Infection
• Immunologic Deficiency Syndromes
• Infection
• Infection, Human Immunodeficiency Virus I

Intervention

Drug:
• Physician determined comparator PI + ritonavir

• GW640385 + ritonavir

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Darlinghurst	New South Wales
Australia	GSK Investigational Site	Liverpool	New South Wales
Australia	GSK Investigational Site	South Yarra	Victoria
Belgium	GSK Investigational Site	Bruxelles
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Sainte-Foy	Quebec
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Vancouver	British Columbia
France	GSK Investigational Site	Caen
France	GSK Investigational Site	La Roche Sur Yon cedex 9
France	GSK Investigational Site	Lyon Cedex 02
France	GSK Investigational Site	Lyon Cedex 03
France	GSK Investigational Site	Nantes
France	GSK Investigational Site	Paris Cedex 10
France	GSK Investigational Site	Paris Cedex 12
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Bonn	Nordrhein-Westfalen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Muenchen	Bayern
Italy	GSK Investigational Site	Bagno a Ripoli (FI)	Toscana
Italy	GSK Investigational Site	Bari	Puglia
Italy	GSK Investigational Site	Ferrara	Emilia-Romagna
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Pavia	Lombardia
Italy	GSK Investigational Site	Rimini	Emilia-Romagna
Italy	GSK Investigational Site	Torino	Piemonte
Portugal	GSK Investigational Site	Cascais
Portugal	GSK Investigational Site	Lisboa
Puerto Rico	GSK Investigational Site	Ponce
Puerto Rico	GSK Investigational Site	San Juan
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Constanta
Romania	GSK Investigational Site	Iasi
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United States	GSK Investigational Site	Bakersfield	California
United States	GSK Investigational Site	Baltimore	Maryland
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Bradenton	Florida
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Denver	Colorado
United States	GSK Investigational Site	Denver	Colorado
United States	GSK Investigational Site	Fort Lauderdale	Florida
United States	GSK Investigational Site	Fort Lauderdale	Florida
United States	GSK Investigational Site	Fort Lauderdale	Florida
United States	GSK Investigational Site	Fountain Valley	California
United States	GSK Investigational Site	Greenville	South Carolina
United States	GSK Investigational Site	Hampton	Virginia
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Indianapolis	Indiana
United States	GSK Investigational Site	Las Vegas	Nevada
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Louisville	Kentucky
United States	GSK Investigational Site	Miami Beach	Florida
United States	GSK Investigational Site	Newark	New Jersey
United States	GSK Investigational Site	Norwalk	Connecticut
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Rochester	New York
United States	GSK Investigational Site	San Francisco	California
United States	GSK Investigational Site	San Francisco	California
United States	GSK Investigational Site	Washington, D.C.	District of Columbia
United States	GSK Investigational Site	Washington, D.C.	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
ViiV Healthcare

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Germany,  Italy,  Portugal,  Puerto Rico,  Romania,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time averaged change in plasma HIV-1 RNA over 16 wks
Primary	Proportion of subjects achieving the target pharmacokinetic (PK) GW640385 drug levels
Primary	Change in laboratory parameters
Secondary	Assessments of HIV viral load changes
Secondary	GW640385 and RTV pharmacokinetic measurements
Secondary	The incidence of adverse events
Secondary	Changes in laboratory measurements
Secondary	ECG measurements
Secondary	HIV viral resistance assessment
Secondary	Immunologic measures