Treatment of HIV-1 infections
Conditions
Interventions
Product Name: GW873140
Product Code: GW873140
Pharmaceutical Form: Film-coated tablet
CAS Number: 461023-63-2
Current Sponsor code: GW873140
Concentration unit: mg milligram(s)
Concentration type: equ
Sponsors
GlaxoSmithKline Research and Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.HIV-1 infected subjects aged 18 years or older. Females must fall into one of the following categories: •Non-childbearing potential: defined as women who are surgically sterile or post-menopausal •Childbearing potential: has a negative pregnancy test result (?-human chorionic gonadotropin; ?-HCG) within 35 days prior to administration of investigational product (Day 1) and agrees to use a proven double barrier method of contraception 2.Screening plasma HIV-1 RNA =5000copies/ 3.Total prior antiretroviral experience of at least three months and documented genotypic or phenotypic resistance to at least one compound in each of the following classes of antiretrovirals: NRTIs (includes NtRTI TDF), NNRTIs, and PIs 4.R5-tropic virus according to viral tropism assessment at screening 5.Current receipt of an unchanged “pre-study” ART regimen for at least four weeks prior to screening; 6.Subjects must be able to receive a RTV-boosted PI as part of their OBT regimen. 7.Ability to understand and comply with protocol requirements, instructions and protocol-stated restrictions. 8.Signed and dated written informed consent prior to initiation of pre-baseline study procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Plasma sample tests as R5/X4 tropic, X4-tropic only, or non-phenotypeable based on viral tropism assessment at screening. 2.Any acute laboratory abnormality at screening 3.Subjects that make any changes to their ART regimen during the period beginning four weeks prior to screening until Day 1. 4.Significant blood loss (=500mL) within 56 days prior to screening 5.Pregnant or lactating women. 6.Previous participation in an experimental drug and/or vaccine trial(s) within 30 days or 5 half-lives, or twice the duration of the biological effect of the experimental drug or vaccine - whichever is longer, prior to screening for the study. 7.Subjects with any prior receipt of an investigational CCR5 or CXCR4 antagonist are excluded. 8.Any clinically significant finding on screening or baseline ECG. 9.History of clinically relevant pancreatitis or hepatitis within the previous 6 months. Asymptomatic individuals with chronic hepatitis B (HBV) or hepatitis C virus (HCV) infection will not be excluded 10.Any condition which, may interfere with the subject’s ability to comply with the dosing schedule and/or protocol evaluations or which might compromise the safety of the subject. 11.Any evidence of active CDC Class C conditions or opportunistic infections. Subjects on stable, anti-infective treatment or prophylaxis regimen are allowed in the study provided the therapy is not specifically prohibited 12.Any condition which, might interfere with the ADME of the drug. 13.History of a drug or other allergy which, contraindicates the subject’s participation in the study or known hypersensitivity to any study medication or excipients. 14.Treatment with radiation therapy or cytotoxic chemotherapeutic agents within 30 days of investigational product administration or anticipated need for such treatment during the study 15.Current severe illness, including liver and renal failure, major organ allograft, malignancy requiring parenteral chemotherapy that can not be discontinued for the duration of the trial, or any other conditions which would make the subject unsuitable for the study. 16.Use of systemic immunosupressants and/or immunomodulators within 30 days prior to study Day 1 17.Anticipated continued need for prescription or over-the-counter (OTC) medications that are on the prohibited medication list within 30 days prior to study Day 1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To demonstrate the superiority of GW873140 400mg BID plus optimised background therapy (OBT) compared to placebo plus OBT, as measured by the difference in plasma HIV-1 RNA average area under the curve minus baseline (AAUCMB) between the two treatment arms at 24 and 48 weeks.;Secondary Objective: •demonstrate superiority as measured by the proportion of responders with sustained plasma HIV-1 RNA <400copies/mL, defined by the outcomes of TLOVR •assess antiviral activity as measured by •Proportion with sustained plasma HIV-1 RNA <50copies/mL •Estimated TLOVR based on plasma HIV-1 RNA <400 and <50copies/mL •Proportion of subjects with a Ctau1.0 log10 copies/mL decrease in plasma HIV-1 RNA from baseline. •evaluate safety and tolerability, impact on CD4 cell counts and immunologic markers ,HIV disease progression,qualitative changes in viral tropism and development of antiretroviral resistance to GW873140 and other on-study drugs •explore relationships between baseline HIV-1 resistance to on-study drugs and antiviral response. •evaluate plasma PK of GW873140 400mg BID when used in combination with OBT •explore how bothersome certain symptoms are for and how symptoms impact on health related quality of life. •evaluate adherence. ;Primary end point(s): •Antiviral activity of GW873140 400mg BID plus OBT versus placebo plus OBT, following 24 and 48 weeks of treatment as measured by plasma HIV-1 RNA AAUCMB. | — |
Countries
Austria, Denmark, Germany, Hungary, Ireland, United Kingdom
Outcome results
None listed