GW873140 to Treat HIV-1 Infected Adults

NCT00076284 | Completed Phase 2

• 2 other identifiers: 04008704-I-0087
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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 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.

Conditions

HIV Infections

Keywords

CCR5 Antagonist; Coreceptor Inhibitor; Fusion Inhibitor; Entry Inhibitor; Antiretroviral; HIV

Interventions

GW873140 DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy adult male aged greater than or equal to 18 OR
• Healthy adult female aged greater than or equal to 18, of non-childbearing potential, defined as: Women who are surgically sterile or are post-menopausal, as indicated by history of no menses for a minimum of one year from the date of the screening visit.
• Healthy adult female aged greater than or equal to 18 of childbearing potential, who agrees to use double barrier method (e.g. condom+diaphragm) starting from the screening visit through the follow up visit (Day 24).
• Note: Spermicides and/or hormonal contraceptives will not be considered sufficient forms of contraception for this study.
• Screening plasma HIV-1 RNA greater than or equal to 5,000- less than or equal to 250,000 copies/mL.
• Viral load within the past 30-90 days of the screening visit must be within 0.5log of screening HIV-1 RNA.
• Not taken any antiretroviral therapy for the preceding 3 months from screening visit.
• CD4 cell count greater than or equal to 200 cells/mm(3) with a historical nadir greater than or equal to 200 cells/mm(3).
• CCR5-tropic virus based on viral tropism assessment at screening visit.
• Normal resting 12-lead electrocardiogram at screening visit.
• Signed and dated written informed consent prior to admission to the study.
• Willingness and ability to fast for 10 hours except for water from 9:00 p.m. until 7:00 a.m. during eight of the study days.
• Willingness and ability to eat a 30% fat diet during the 10 day treatment period of the study.
• Willingness to allow stored blood samples to be used in the future for further testing or for studying HIV disease and immune function.

You may not qualify if:

• CXCR4 tropic virus based on viral tropsin assessment at screening visit.
• Chronic diarrhea (greater than 3 stools/day)
• Subject with history of oropharyngeal candidiasis or C AIDS-defining illness according to the 1993 Centers for Disease Control (CDC) AIDS surveillance definition.
• Greater than two prior ARV regimens.
• Any acute laboratory abnormality at screen which, in the opinion of the investigator, should preclude the subject's participation in the study of an investigational compound. Any grade 4 laboratory abnormality at screen will exclude a subject from study participation unless the investigator can provide a compelling explanation for the laboratory result(s) and has the assent of the sponsor.
• Significant blood loss (1 pint of whole blood) within 56 days of the screening visit of the study.
• Previous participation in an experimental drug trial(s) within 30 days of the screening visit of the study.
• Any conduction delay, regardless of clinical significance on screening ECG.
• History of clinically relevant pancreatitis or hepatitis within the previous 6 months.
• Any condition which, in the opinion of the investigator, may interfere with the subject's ability to comply with the dosing schedule and protocol evaluations (including alcohol or drug abuse) or which might compromise the safety of the subject.
• Any condition which, in the opinion of the investigator, might interfere with the absorption, distribution, metabolism or excretion of the drug such as diabetes mellitus, hyperthyroidism, malabsorption syndrome, etc.
• History of cholecystectomy, cholelithiasis or cholecystitis.
• Any immunization within 30 days prior to first dose of investigational product.
• History of a drug or other allergy which in the opinion of the investigator, contraindicates the subject's participation in the study or known hypersensitivity to any study medication.
• Treatment with radiation therapy or cytotoxic chemotherapeutic agents within 30 days of investigational product administration or anticipated need for such treatment within the study.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institute of Allergy and Infectious Diseases (NIAID)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 7630250 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.

  PMID: 10961858 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.

  PMID: 10975604 BACKGROUND

MeSH Terms

Conditions

HIV Infections

Interventions

aplaviroc

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: January 16, 2004
• First Posted: January 19, 2004
• Study Start: January 1, 2004
• Study Completion: March 1, 2005
• Last Updated: March 4, 2008

Record last verified: 2005-03

Locations

US (1)