Treatment of HIV-1 infection
Conditions
Interventions
Product Name: GW873140
Product Code: GW873140
Pharmaceutical Form: Film-coated tablet
CAS Number: 461023-63-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
P
Sponsors
GlaxoSmithKline Research and Development
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 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/mL There are no CD4 cell count entry restrictions, however investigators must exercise clinical discretion 3.Total prior antiretroviral experience of at least 3 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/X4-tropic virus according to viral tropism assessment at screening 5.Current unchanged “pre-study” ART regimen for at least four weeks prior to screening; this pre-study regimen may be no ART. Subjects must remain on this regimen until randomization (Day 1). 6.Subjects must be able to receive a RTV-boosted PI as part of their OBT regimen. The drugs in the OBT regimen will be chosen from the locally available antiretrovirals and must consist of between three and six drugs, one of which must be a RTV-boosted PI. 7.Ability to understand and comply with protocol requirements 8.Signed and dated written informed consent 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) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Plasma sample tests as R5-tropic only, 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 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 dosing schedule and/or protocol evaluations or might compromise safety of subject. 11.Any evidence of active CDC Class C conditions or opportunistic infections. 12.Any condition which might interfere with ADME of drug. 13.History of a drug or other allergy or known hypersensitivity to any study medication or excipients. 14.Treatment with radiation therapy or cytotoxic chemotherapeutic agents within 30 days administration 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: •Assess antiviral activity of GW873140 400mg BID plus OBT compared to PBO plus OBT as measured by: •Proportion with sustained plasma HIV-1 RNA <400 and <50copies/mL,. •Estimated TLOVR based on plasma HIV-1 RNA <400 and <50copies/mL •Proportion of subjects with a ?1.0 log10 copies/mL decrease in plasma HIV-1 RNA from baseline •Evaluate safety and tolerability, immunologic markers, HIV disease progression, 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 qualitative changes in viral tropism •Evaluate plasma PK of GW873140 400mg BID when used in combination with OBT. •Explore how bothersome certain symptoms are and how symptoms impact on health related QofL. •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
Denmark, Germany, Hungary, Ireland, United Kingdom
Outcome results
None listed