Clinical trial NCT00197145: Study Of Chemokine Coreceptor 5 (CCR5) Antagonist GW873140 In R5-Tropic Treatment-Experienced HIV-Infected Subjects
Official title: A Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel Group Study to Compare the Efficacy and Safety of GW873140 400mg BID in Combination With a Ritonavir-containing Optimized Background Therapy (OBT) Regimen Versus Placebo Plus OBT Over 48 Weeks.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Infection, Human Immunodeficiency Virus I
Keywords: HIV-1 GW873140 CCR5 antagonist experienced
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2005-09-20
Enrollment: 24
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: The purpose of this study is to evaluate the safety and efficacy of the CCR5 antagonist GW873140 or placebo in combination with an optimized background regimen in treatment-experienced HIV-infected subjects with R5-tropic virus


Eligibility criteria: Inclusion Criteria:

* HIV-infected.
* Screening viral load at least 5000copies/mL.
* R5-tropic only virus at screening.
* Total prior antiretroviral experience of at least 3 months and documented resistance to at least one drug in each of the following classes: nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), and protease inhibitors (PI).
* Stable antiretroviral regimen (or no antiretroviral treatment) for at least 4 weeks before screening.
* Able to receive a ritonavir-boosted protease inhibitor during treatment studies.
* Women of childbearing potential must use specific forms of contraception.

Exclusion criteria:

* Acute laboratory abnormalities.
* History of pancreatitis or hepatitis, hepatitis B or hepatitis C coinfection, or any chronic liver disease. Screening liver function tests will be used to determine eligibility.
* R5/X4-tropic, X4-tropic only, or non-phenotypeable virus at screening.
* Changes to antiretroviral therapy from 4 weeks prior to screening until Day 1 of treatment study.
* Pregnancy or breastfeeding women.
* Recent participation in an experimental drug trial.
* Prior use of a CCR5 or CXCR4 antagonist.
* Significant ECG abnormalities or significant history of active pancreatitis, hepatitis, opportunistic infections, malabsorption disorders, cancer, or severe illness.
* Current use of certain medications may exclude participation in this study.
* Additional qualifying criteria and laboratory test requirements to be assessed by study physician.

Primary outcomes:
measure: Number of Participants With Plasma HIV-1 RNA <400 Copies Per Milliliter (Copies /mL) at Week 24 and 48
timeFrame: Week 24
measure: Average Area Under the Curve Minus Baseline (AAUCMB) of Plasma HIV-1 RNA Through the Entire Study Period
timeFrame: Up to Week 40
measure: Number of Participants With >= 1.0 log10 Copies/mL Decrease in Plasma HIV-1 RNA From Baseline Over Time
timeFrame: Day 1 up to Week 12 Follow-up of the Randomized Treatment phase, up to Week 12 Follow-up of the Open Labeled Non-Randomized phase and every 6 months Follow-up of off study drug/on study phase
Secondary outcomes:
measure: Number of Participants With Plasma HIV-1 RNA <50 Copies/mL at Week 24 and 48
timeFrame: Week 24
measure: Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE), Death, Drug-related AE and AE Leading to Treatment Discontinuation
timeFrame: Up to Follow-up (Week 52)
measure: Number of Participants With Treatment Emergent Laboratory Abnormalities for Chemistry Data at Any Visit Post-Baseline
timeFrame: Up to Week 40
measure: Change From Baseline in Chemistry Parameters of ALT, ALP, AST and CK During the Randomized Treatment Phase
timeFrame: Baseline (Day 1), Week 12 and Week 24
measure: Change From Baseline in Chemistry Parameters of CO2 Content/Bicarbonate, Chloride, Cholesterol, Glucose, High DL Cholesterol, LDL Cholesterol, Triglycerides, Potassium, Urea and Sodium During the Randomized Treatment Phase
timeFrame: Baseline (Day 1), Week 12 and Week 24
measure: Change From Baseline in Chemistry Parameter of Creatinine and Total Bilirubin During the Randomized Treatment Phase
timeFrame: Baseline (Day 1), Week 12 and Week 24
measure: Change From Baseline in Chemistry Parameter of Albumin During the Randomized Treatment Phase
timeFrame: Baseline (Day 1), Week 12 and Week 24
measure: Change From Baseline in Chemistry Parameter of Lipase During the Randomized Treatment Phase
timeFrame: Baseline (Day 1), Week 12 and Week 24
measure: Change From Baseline in Haematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, White Blood Cell (WBC) Count During the Randomized Treatment Phase
timeFrame: Baseline (Day 1), Week 12 and Week 24
measure: Change From Baseline in Haematology Parameter of Mean Corpuscle Volume (MCV) During the Randomized Treatment Phase
timeFrame: Baseline (Day 1), Week 12 and Week 24
measure: Change From Baseline in Haematology Parameter of Hematocrit During the Randomized Treatment Phase.
timeFrame: Baseline (Day 1), Week 12 and Week 24
measure: Change From Baseline in Haematology Parameter of Hemoglobin During the Randomized Treatment Phase
timeFrame: Baseline (Day 1), Week 12 and Week 24
measure: Change From Baseline in Electrocardiograph (ECG) Parameter of Heart Rate (HR) During the Randomized Treatment Phase
timeFrame: Baseline (Day 1), Week 4 and Week 24
measure: Change From Baseline in ECG Parameter of RR Interval, Uncorrected QT Interval, QTc Interval (Fridericia), QTc Interval (Bazette), PR Interval and QRS Duration During the Randomized Treatment Phase
timeFrame: Baseline (Day 1), Week 4 and Week 24
measure: Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Counts During the Randomized Treatment Phase
timeFrame: Baseline (Day 1), Week 12, Week 24 and Week 40
measure: Time to Centres for Disease Control and Prevention (CDC) Class C Acquired Immune Deficiency Syndrome (AIDS)-Defining Event or Death
timeFrame: Up to Week 12 Follow-up of the Randomized phase, up to Week 12 Follow-up of the Open Labeled Non-Randomized phase and every 6 months Follow-up of off study drug/on study phase
measure: Number of Participants With Development of Antiretroviral Resistance to GW873140 400 mg BID and Other Antiretroviral Drugs
timeFrame: Up to Follow-up (Week 52)
measure: Number of Participants With 50% Inhibitory Concentration (IC50) Fold Resistance at Baseline
timeFrame: Baseline (Day 1)
measure: Plasma GW873140 400 mg BID Pharmacokinetic (PK) Parameter of Area Under the Plasma Concentration-time Curve During One Dosing Interval of Length (Tau) (AUC [0-tau]) During the Randomized Treatment Phase
timeFrame: Week 4 (pre-dose [0 hour], 1, 2, 3, 4, 6, 8, 10 hour post-evening dose), Week 12 (pre-dose [0 hour] and 2-4 hour post-morning dose) and Week 24 (pre-dose and 2-4 hour post-morning dose)
measure: Plasma GW873140 400 mg BID PK Parameter of Maximum Observed Plasma Concentration (Cmax) During the Randomized Treatment Phase
timeFrame: Week 4 (pre-dose [0 hour], 1, 2, 3, 4, 6, 8, 10 hour post-evening dose), Week 12 (pre-dose [0 hour] and 2-4 hour post-morning dose) and Week 24 (pre-dose and 2-4 hour post-morning dose)
measure: Plasma GW873140 400 mg BID PK Parameter of Time of Maximum Observed Plasma Concentration (Tmax) During the Randomized Treatment Phase
timeFrame: Week 4 (pre-dose [0 hour], 1, 2, 3, 4, 6, 8, 10 hour post-evening dose), Week 12 (pre-dose [0 hour] and 2-4 hour post-morning dose) and Week 24 (pre-dose and 2-4 hour post-morning dose)
measure: Plasma GW873140 400 mg BID PK Parameter of Concentration at End of Dosing Interval (Trough Concentration [Cτ]) During the Randomized Treatment Phase
timeFrame: Week 4 (pre-dose [0 hour], 1, 2, 3, 4, 6, 8, 10 hour post-evening dose), Week 12 (pre-dose [0 hour] and 2-4 hour post-morning dose) and Week 24 (pre-dose and 2-4 hour post-morning dose)
measure: Investigational Product Adherence Measured by Pill Counts
timeFrame: Up to Week 48 of Randomized Treatment phase and up to Switch + 24 Weeks of the Open Labeled phase
measure: Number of Participants Who Were Bothered by Each of Several Specific Symptoms Evaluated Using the HIV Symptom Index Questionnaire During the Randomized Treatment Phase
timeFrame: Upto Week 48
measure: Number of Participants With the Impact on Health Related Quality of Life Measured by Euro Quality of Life (Qol) Questionnaire During the Randomized Treatment Phase
timeFrame: Up to Week 48
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Beverly Hills
country: United States
facility: GSK Investigational Site
state: California
city: Fountain Valley
country: United States
facility: GSK Investigational Site
state: California
city: Laguna Beach
country: United States
facility: GSK Investigational Site
state: California
city: Long Beach
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Oakland
country: United States
facility: GSK Investigational Site
state: California
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: Tarzana
country: United States
facility: GSK Investigational Site
state: California
city: Glastonbury
country: United States
facility: GSK Investigational Site
state: Connecticut
city: Norwalk
country: United States
facility: GSK Investigational Site
state: Connecticut
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
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 Myers
country: United States
facility: GSK Investigational Site
state: Florida
city: Key West
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Oakland Park
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Plantation
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Decatur
country: United States
facility: GSK Investigational Site
state: Georgia
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Wichita
country: United States
facility: GSK Investigational Site
state: Kansas
city: New Orleans
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Portland
country: United States
facility: GSK Investigational Site
state: Maine
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Minneapolis
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: East Orange
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Hillsborough
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Newark
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Mount Vernon
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Charlotte
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Akron
country: United States
facility: GSK Investigational Site
state: Ohio
city: Portland
country: United States
facility: GSK Investigational Site
state: Oregon
city: Portland
country: United States
facility: GSK Investigational Site
state: Oregon
city: Columbia
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Annandale
country: United States
facility: GSK Investigational Site
state: Virginia
city: Hampton
country: United States
facility: GSK Investigational Site
state: Virginia
city: Lynchburg
country: United States
facility: GSK Investigational Site
state: Virginia
city: Spokane
country: United States
facility: GSK Investigational Site
state: Washington
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Ponce
country: Puerto Rico
facility: GSK Investigational Site
city: San Juan
country: Puerto Rico
facility: GSK Investigational Site
Study officials:
affiliation: ViiV Healthcare
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: