GW873140 to Treat HIV-1 Infected Adults
|First Submitted Date ICMJE||January 16, 2004|
|First Posted Date ICMJE||January 19, 2004|
|Last Update Posted Date||March 4, 2008|
|Start Date ICMJE||January 2004|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00076284 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||GW873140 to Treat HIV-1 Infected Adults|
|Official Title ICMJE||A Phase II, Double-Blind RAndomized, Placebo-Controlled Study to Evaluate the Antiviral Activity, Safety, Tolerability, and Pharmacokinetics of GW873130 for 10 Days in HIV-1 Infected Adults|
This study will determine which of four doses of GW873140 can safely be given to adults to lower the amount of virus (HIV-1) in the body. GW873140 is a new type of anti-HIV drug called a CCR5 receptor antagonist. CCR5 is a receptor on T cells (a type of white blood cell) where HIV-1 enters and then infects the cell. GW873140 is intended to block the CCR5 receptor so that HIV-1 cannot enter the cell.
HIV-1-infected patients 18 years of age and older may be eligible for this study. Candidates are screened with a medical history and physical examination, electrocardiogram, and blood and urine tests. Some of the blood drawn is used to test the patient's HIV-1 type to see if the study drug might lower the amount of HIV-1 in the blood. Women who can become pregnant have a pregnancy test.
Participants are hospitalized for 12 days. They are randomly assigned to take one of the following four treatments for 10 days: 1) 200 mg of GW873140 once a day, or placebo (a look-alike pill with no active ingredient); 2) 200 mg of GW873140 twice a day, or placebo; 3) 400 mg of GW873140 once a day, or placebo; or 600 mg of GW873140 twice a day, or placebo. Participants record the meals they eat on a diary card. In addition, they undergo the following tests and procedures:
Follow-up visit (2 weeks after last drug dose--day 24)
The development of resistance to all currently marketed drugs for HIV infection has been observed and is a major reason for failure of therapy. In particular, there is a great need for drugs against new targets and having novel mechanisms of action against new targets. Most of the currently approved drugs are targeted toward the inhibition of viral enzymes. However, the process of viral entry and fusion has become an active area of research. Among the steps involved in viral entry, binding of HIV to CD4 co-receptors on the cell surface is an important and promising target for new drug development.
GW873140 is a CCR5 antagonist that is in Phase I clinical development as a viral entry inhibitor for the treatment of HIV infection. GW873140 has demonstrated in vitro antiviral activity with an IC50 against CCR5-tropic HIV-1 of 1nM equals about 0.5ng/mL), that is shifted 8-10 fold (10nM equals about 0.5ng/mL) in the presence of physiological concentrations of human plasma proteins. A study to investigate the safety, tolerability, and pharmacokinetics of escalating single (50-1200mg) and repeat (200-800mg BID) doses of GW873140 has been conducted in 70 healthy volunteers (GW873140/001). Preliminary results indicate that GW873140 is well-tolerated up to a dose of 1200 mg following single dose and 800 mg BID following multiple-dose. Additionally, food was shown to increase the AUC and Cmax of a 400 mg single dose by 1.7-and 2.2-fold, respectively.
Concentrations above the protein binding corrected IC90 are achieved following oral dosing and in vivo binding studies in healthy subjects demonstrate greater than 97% receptor occupancy 2 and 12 hours after multiple doses and 68-88% receptor occupancy 24 hours after a single dose, despite plasma concentrations below or near detectable limits.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 2|
|Study Design ICMJE||Primary Purpose: Treatment|
|Condition ICMJE||HIV Infections|
|Intervention ICMJE||Drug: GW873140|
|Study Arms||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Estimated Completion Date||March 2005|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
A subject will be eligible for inclusion in this study only if all of the following criteria apply:
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
Medications that are not approved on this list, will need to be discontinued 7 days prior to first dose of investigational product (for drugs that are non-hepatic inducers) and 30 days prior to first dose of investigational product (for drugs that are hepatic inducers) through 5 days post dose.
To clarify the exclusion of patients with hepatitis and pancreatitis, the following patients will be excluded:
Patients with evidence of chronic hepatitis B or C are not excluded from study participation if they are clinically asymptomatic, liver enzymes are less than five times normal, and they have no evidence of hepatic synthetic dysfunction (i.e. PT less than 1.5 times upper limit of normal).
|Ages||Child, Adult, Senior|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00076284|
|Other Study ID Numbers ICMJE||040087
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Institute of Allergy and Infectious Diseases (NIAID)|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|PRS Account||National Institutes of Health Clinical Center (CC)|
|Verification Date||March 2005|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP