Treatment of heavily pretreated patients
Conditions
Interventions
Trade Name: TELZIR
Product Name: Telzir
Product Code: GW433908
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: fosamprenavir
Current Sponsor code: GW433908
Concentration unit: mg milligra
Sponsors
GlaxoSmithKline, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adult male and female PI-experienced HIV-infected subjects =18 years. 2. Three antiretroviral class (N(t)RTI, NNRTI and PI) therapy experienced subjects 3. =2 prior PI-based regimen with a documented history of virological failure (a confirmed plasma HIV-1 RNA concentration of ? 400 copies/mL) 4. Documented evidence of a viral genotype with at least one primary protease mutation other than the D30N. 5. HIV-1 RNA assay =1000 copies/mL at screening 6. No antiretroviral therapy (ART) modifications between Screening and Day 1. 7. A female subjects is eligible to enter and participate in the study if she is of: a Non-childbearing potential (ie, physiologically incapable of becoming pregnant, including any female who is pre-menarchal or post-menopausal); b Childbearing potential, has a negative serum beta human chorionic gonadotropin (beta-HCG, pregnancy) test at screen and negative urine pregnancy test at Day 1 and who agrees to use one of the following methods of contraception (any contraception method must be used consistently and correctly, i.e., in accordance with both the approved product label and the instructions of a physician): ? Complete abstinence from intercourse from 2 weeks prior to administration of the investigational products or permitted substitution medications, throughout the study, and for at least 2 weeks after discontinuation of all investigational products or permitted substitution medications; ? Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide); ? Any intrauterine device (IUD) with published data showing that the expected failure rate is =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subjects with virus harboring the I50V mutation, the V32I with I47V mutations or six or more of the following PRO mutations in the screening genotype (APV/RTV resistance algorithm): L10F/I/V, K20M/R, E35D, R41K, I54V, L63P, V82A/F/T/S or I84V 2. Subjects with virus harboring eight or more of the following PRO mutations in the screening genotype (LPV/RTV mutation score [Kempf et al., 2001]): L10F/I/R/V, K20M/R, L24I, M46I/L, F53L, I54L/T/V, L63P, A71I/L/T/V, V82A/F/T, I84V, or L90M 3. Known non-adherence as key cause for detectable viral load 4. Planned use of NNRTIs as part of the study salvage regimen 5. Planned use of atazanavir or hydroxyurea as part of the study salvage regimen 6. Evidence of current active hepatitis or any clinically relevant hepatitis within 28 days prior to entry. 7. History of clinically relevant pancreatitis or any clinically relevant hepatitis within the last 6 months. 8. If, in the opinion of the examining physician, an unstable hepatic, cardiovascular, renal, pulmonary, endocrine, metabolic, neurological, haematological, or gastrointestinal condition is present or any other medical condition which the investigator considers sufficiently serious to interfere with the conduct, completion, or results of this trial or constitutes an unacceptable risk to the subject. 9. Subject has any acute laboratory abnormality at screening, which, in the opinion of the investigator, would preclude the subject’s participation in the study of an investigational compound. 10. Any grade 4 laboratory abnormality would exclude a subject from study participation 11. Subject has an active or acute CDC Clinical Category C event at screening. Treatment for the acute event must have been completed at least 30 days prior to screening. 12. Subject is enrolled in one or more investigational drug protocols, which may impact HIV RNA suppression 13. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5 times the upper limit of normal (ULN) within 28 days prior to Day 1. 14. Total bilirubin >2.5 times ULN within 28 days prior to Day 1. 15. Subject has an estimated creatinine clearance <60 mL/min via the Cockcroft-Gault method. NOTE: Creatinine clearance should be estimated using the following formula: - For serum creatinine concentration in mg/dL: - ((140-age)(weight in kg)/ serum creatine x 72 ) x (0.85 for women only) - For serum creatinine concentration in µmol/L: - ((140-age)(weight in kg) / serum creatine x 0.8) x (0.85 for women only) 16. Subjects who require treatment with any of the following medications within 28 days of commencement of investigational product, or an anticipated need during the study: ? Amiodarone, astemizole, bepridil, cisapride, dihydroergotamine, ergonovine, ergotamine, flecainide, halofantrine, lidocaine, lovastatin, methylergonovine, midazolam, pimozide, propafenone, quinidine, simvastatin, terfenadine, triazolam (these drugs have been excluded due to potential drug interactions with either FPV, LPV and/or RTV leading to safety problems) ? Carbamazepine, dexamethasone, phenobarbital, phenytoin, primidone, rifampin, St Johns Wort (Hypericum perforatum), troglitazone (these drugs have been excluded because they have the potential to decrease plasma protease inhibitor concentrations). ? Investigators should consult the most current prescribing information for each Investigational product for medications that are "Contraindicated" as well as Section 8.2 "Prohibited Medications" 17. Subject
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: ? To test the superiority of the increased FPV dose (FPV/RTV 1400mg/100mg BID; Group B) and the dual boosted PI combination FPV/LPV/RTV (700mg/533mg/133mg BID) based therapy (Group C) over the standard FPV/RTV (700mg/100mg BID) based therapy (Group A) as measured by the average area under the curve minus baseline [AAUCMB] in plasma HIV-1 RNA at 24 weeks when each are administered in combination with an optimised background therapy, in a multiple PI-experienced population experiencing virological failure. ;Secondary Objective: To compare the antiviral response of the increased FPV dose (Group B) and FPV/LPV/RTV based therapy (Group C) versus the standard FPV/RTV based therapy (Group A) over 24 weeks of therapy; To compare the safety and tolerability of Group B and Group C versus Group A over 24 weeks of therapy; To compare the occurrence of events related to metabolic abnormalities of Group B and Group C versus Group A over 24 weeks of therapy; To compare the immunologic response of Group B and Group C versus Group A over 24 weeks of therapy; To characterise steady-state plasma APV trough concentrations and, where applicable, LPV trough concentrations; To evaluate the impact of absolute values in GIQ on virological outcome at Week 24; To assess viral resistance patterns at baseline and those which emerge in subjects with virological failure, and to correlate these patterns with treatment outcome.;Primary end point(s): The primary efficacy endpoint is the average area under the curve minus baseline (AAUCMB) in log10 plasma HIV-1 RNA at Week 24. | — |
Countries
Germany, Italy, Spain, United Kingdom
Outcome results
None listed