A Phase III, Randomized, Controlled, Open-label, Multicentre, Three Arm Study to Compare the Efficacy and Safety of a Dual-boosted HIV-1 Protease Inhibitor (PI) regimen of Fosamprenavir (FPV)/ Lopinavir (LPV)/Ritonavir (RTV)/1400mg/533mg/133mg Twice Daily (BID) and an Increased Dosage Regimen of FPV/RTV 1400mg/100mg BID Versus the Standard Dosage Regimen of FPV/RTV 700mg/100mg BID for 24 Weeks in Multiple-PI Experienced, HIV-infected Adults Experiencing Virological Failure

• Conditions: Treatment of heavily pretreated patients

• Registration Number: EUCTR2004-003827-10-DE
• Lead Sponsor: GlaxoSmithKline R&D

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2004-12-29
• Last Update Posted: 10 February 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 150

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 <1% per year;
? Sterilization (female subject or male partner of female subject).
Hormonal contraception is not acceptable for inclusion into this study.
All subjects participating in this study should be counselled on the practice of safe sex.
8. The subject is able to understand and comply with protocol requirements and instructions and is likely to complete the study as planned.
9. Subject or subject’s legal representative is willing and able to understand and provide written informed consent prior to participation in this study
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

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified