Ignite Creation Date:
2024-05-05 @ 11:33 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00076284
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
2004-01-16
Brief Title:
GW873140 to Treat HIV-1 Infected Adults
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
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
Status:
COMPLETED
Status Verified Date:
2005-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 patients 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 123458 and 10
Review of any HIV-associated conditions other medications taken besides the study drug and well-being days 12345810 and 11
Check of vital signs including blood pressure pulse and temperature days 1234567810 and 11
Weight assessment days 1 and 10
Electrocardiogram to measure the electrical activity of the heart days 1238 and 10
Blood draws for routine laboratory tests to measure T-cell counts and to measure HIV levels days 12510 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
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 patients 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 123458 and 10
Review of any HIV-associated conditions other medications taken besides the study drug and well-being days 12345810 and 11
Check of vital signs including blood pressure pulse and temperature days 1234567810 and 11
Weight assessment days 1 and 10
Electrocardiogram to measure the electrical activity of the heart days 1238 and 10
Blood draws for routine laboratory tests to measure T-cell counts and to measure HIV levels days 12510 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
Detailed Description:
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 05ngmL that is shifted 8-10 fold 10nM equals about 05ngmL 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 GW873140001 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 17-and 22-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
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 05ngmL that is shifted 8-10 fold 10nM equals about 05ngmL 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 GW873140001 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 17-and 22-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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 04-I-0087 | None | None | None |