A Phase IIB, Randomized, Multicenter, Parallel Group Study to Evaluate the Short-Term Safety, Pharmacokinetics and Antiviral Activity of Four Blinded Dosing Regimens of GW640385/Ritonavir Therapy Compared to Open-label Current Protease Inhibitor (PI) therapy in HIV-1 Infected, PI Experienced Adults for 2 weeks with Long-Term Evaluation (> 48 weeks) of Safety, Pharmacokinetic and Antiviral Activity of Selected GW640385/RTV Dosing Regimen(s) vs. a Ritonavir-boosted, PI Containing Regime

• Conditions: Treatment of HIV-1 infection.

• Registration Number: EUCTR2005-001150-24-PT
• Lead Sponsor: GlaxoSmithKline Research & Development Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-10-12
• Last Update Posted: 24 April 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 105

Inclusion Criteria

A subject will be eligible for inclusion in this study only if all of the following criteria apply:
1.HIV-infected adult male aged =18 OR
HIV-infected adult female =18 if she is of:
a.non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is pre-menarchial); or,
b.child-bearing potential with a negative pregnancy test at screen, a negative pregnancy test on Day 1 and who agrees to use one of the methods of contraception listed below. Premenarchial females who develop child-bearing potential while on the study will be expected to follow one of the methods of contraception listed below.
•Agreement for complete abstinence from intercourse from 2 weeks prior to administration of study drugs, throughout the study and for 2 weeks after discontinuation of all study medications. Should a female subject of childbearing potential decide to become sexually active during the course of the study, she must be counseled and be willing to use one of the other contraception methods listed below:
•Double barrier contraception (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide)
•Any intrauterine device (IUD) with published data showing that the expected failure rate is less than 1% per year (not all IUDs meet this criterion)
•Any other method with published data showing that the lowest expected failure rate for that method is less than 1% per year.
Any contraception method must be used consistently and correctly, i.e., in accordance with both the product label and the instructions of a physician. Note: hormonal contraceptives are not considered a sufficient form of contraception for this study. All subjects of childbearing potential or developing child-bearing potential while participating in this study should be counseled on the practice of safe/safer sex.

2.Plasma HIV-1 RNA =1,000 copies/mL at Screening.
3.Evidence of at least two or more multi-PI resistance mutations (L10I/F/V/R, V32I, M46I/L, I54V/L/M, V82A/F/T/S, I84V/A/C, L90M) at Screening or within three months prior to Screening.
4.Subjects currently receiving a regimen that has not changed for at least 8 weeks prior to Screening and which contains a single RTV-boosted PI, excluding TPV/RTV (total daily dose of RTV must be = 200mg)
•In the absence of historic genotypic data confirming eligibility, subject must also have received at least one other PI (with or without RTV) for at least 8 weeks (which may have included TPV/RTV)
5.Ability to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
6.Subject is willing and able to understand and provide signed and dated 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)
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

A subject will not be eligible for inclusion in this study if any of the following criteria apply:
1. Subject requiring a change in their current ART therapy between Screening and Day 1.
2. Current administration of an NNRTI, TPV or dual RTV- boosted PI as part of their ART regimen at Screening.
3. Active CDC HIV-1 Category C disease except cutaneous Kaposi’s Sarcoma not requiring systemic therapy at entry.
4. Pregnant women or women who are breastfeeding.
5. Current or history of thyroid abnormality which requires or has required treatment.
6. History of clinically relevant pancreatitis or hepatitis within the previous 6 months of investigational product administration.
7. Significant blood loss (1 pint of whole blood) within 56 days of the Screening visit.
8. Condition which might interfere with the absorption, distribution, metabolism or excretion of the drug e.g., diabetes mellitus, hyperthyroidism, malabsorption syndrome, chronic diarrhea (>3 stools/day).
9. Condition which 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.
10. History of a drug or other allergy which contraindicates the subject’s participation in the study or known hypersensitivity to the investigational product(s) to be administered in this study
11. Any clinically significant finding on Screening or Day 1 ECG. Includes subjects with any repolarization delay (resting QTcB interval >450 msec at the Screening or Day 1 visit [mean of the three Day 1 values]). Subjects with a history of additional risk factors for torsade de pointes (e.g., heart failure, hypokalemia) will also be excluded.
12. Acute laboratory abnormality at Screening which should preclude the subject’s participation in the study of an investigational compound.
13. Grade 4 laboratory abnormality at Screening with the exception of creatine phosphokinase (CPK). Subjects with an identifiable temporary cause for Grade 4 CPK (e.g. strenuous exercise) may, after consultation with GSK, have a repeat CPK assessment during the Screening period provided it occurs at least 7 days after the initial finding. If on repeat testing the CPK value is = Grade 1, the subject may enter the study providing s/he meets all other eligibility requirements.
14. Grade 3 (5 -10 times upper limit of normal [ULN]) alanine aminotransferase or aspartate aminotransferase within 28 days of Day 1
15. Inadequate renal function at Screening, defined as:
•serum creatinine >1.5mg/dL
•calculated creatinine clearance (CrCl) =60 mL/min
16. Need for use of dual boosted PI, or an NNRTI as part of their background ART (all treatment arms) during the Randomized Phase OR the use of TMC-114 as the Control Arm C boosted-PI from Day 15 until the subject enters the Non-Randomized Phase of the study.
Note: Use of NNRTIs, dual RTV-boosted PIs and TMC-114 will be permitted during the Non-Randomized phase for Control Arm C subjects who have not switched to a 385 containing regimen. For subjects receiving a 385 containing dosing regimen, use of these agents would be dependent on the available drug-drug interaction data that has been communicated to the site.
17. Treatment with other investigational drugs/therapies within 60 days prior to Screening.
18. Subject has received an HIV-1 immunotherapeutic vaccine within 90 days prior to Screening.
19. Treatment with radiation therapy or cytotoxic chemotherapeut

Study & Design

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