GW873140 to Treat HIV-1 Infected Adults

Summary

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: During treatment * Assessment of HIV classification (day 1) * Review of meal diary cards (days 1,2,3,4,5,8, and 10) * Review of any HIV-associated conditions, other medications taken besides the study drug, and well-being (days 1,2,3,4,5,8,10, and 11) * Check of vital signs, including blood pressure, pulse, and temperature (days 1,2,3,4,5,6,7,8,10, and 11) * Weight assessment (days 1 and 10) * Electrocardiogram to measure the electrical activity of the heart (days 1,2,3,8, and 10) * Blood draws for routine laboratory tests, to measure T-cell counts, and to measure HIV levels (days 1,2,5,10, and 11) * Urine tests (days 1 and 10) Post-treatment * Blood tests to monitor the effect of GW873140 on lowering HIV counts (days 12, 15, 17, and 19) Follow-up visit (2 weeks after last drug dose--day 24) * Review of medications taken and general well-being * Check of vital signs * Physical examination * Blood and urine tests.

Timeline

Start

2004-01

Primary completion

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Completion

2005-03

Publications

• Background Arranz M, Collier D, Sodhi M, Ball D, Roberts G, Price J, Sham P, Kerwin R. Association between clozapine response and allelic variation in 5-HT2A receptor gene. Lancet. 1995 Jul 29;346(8970):281-2. doi: 10.1016/s0140-6736(95)92168-0.
• Background Blanpain C, Lee B, Tackoen M, Puffer B, Boom A, Libert F, Sharron M, Wittamer V, Vassart G, Doms RW, Parmentier M. Multiple nonfunctional alleles of CCR5 are frequent in various human populations. Blood. 2000 Sep 1;96(5):1638-45.
• Background Cardon LR, Idury RM, Harris TJ, Witte JS, Elston RC. Testing drug response in the presence of genetic information: sampling issues for clinical trials. Pharmacogenetics. 2000 Aug;10(6):503-10. doi: 10.1097/00008571-200008000-00003.

Drugs

Indications