A randomized, controlled, open-label trial to compare the efficacy, safety and tolerability of TMC114/RTV versus LPV/RTV in treatment-experienced HIV-1 infected subjects.

Conditions: HIV-1 infection
MedDRA version: 9.1Level: LLTClassification code 10020161Term: HIV infection

Registration Number: EUCTR2005-000594-22-DE

Lead Sponsor: Tibotec Pharmaceuticals Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 500

Inclusion Criteria

Note: Re-testing of screening values that lead to exclusion will be allowed only once using an unscheduled visit.

1. Male or female subjects, aged 18 years or older.

2. Subjects with documented HIV-1 infection.

3. Treatment with current HAART regimen for at least 12 weeks.
Note: HAART (Highly Active Antiretroviral Therapy) is defined as potent anti-HIV treatment usually including a combination of three or more drugs with activity against HIV whose purpose is to reduce viral load to undetectable. This regimen usually includes treatment with at least 2 NRTIs in combination with at least 1 additional ARV from the NNRTI and/or PI class.
4. Prescreening and screening plasma HIV-1 RNA > 1000 copies/mL (assayed by RNA PCR standard specimen procedure) on current HAART regimen.
Note: If no documented prescreening viral load is available (taken at least 12 weeks after starting the current HAART regimen), a prescreening visit should be scheduled.
5. Subjects have voluntarily signed the informed consent form.
6. Subjects can comply with the protocol requirements.
7. General medical condition, in the investigator’s opinion, does not interfere with the
assessments and the completion of the trial.
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

Note: Re-testing of screening values that lead to exclusion will be allowed only once using an unscheduled visit

1. Presence of any currently active AIDS defining illness (Category C conditions according to the CDC Classification System for HIV Infection 1993) with the following exceptions:
- Stable cutaneous Kaposi’s Sarcoma (i.e., no internal organ involvement other
than oral lesions) that is unlikely to require any form of systemic therapy during the trial time period.
- Wasting syndrome.
Note: Primary and secondary prophylaxis for an AIDS defining illness is allowed in case the medication used is not part of the disallowed medication.
2. Current or past alcohol and/or drug use which, in the investigator's opinion, could
compromise the subject's safety or adherence to the study protocol procedures.
3. Subjects for whom an investigational ARV is part of the current regimen, with the following exceptions if applicable (depending on local regulatory approval): tenofovir, emtricitabine, atazanavir, fosamprenavir.
Note: Participation in observational studies where no treatment is administered is
allowed (if approved by sponsor).
4. Previous or current use of LPV, enfuvirtide (T-20), tipranavir and TMC114.
5. Use of any non-ARV investigational agents within 90 days prior to screening.
6. Use of disallowed concomitant therapy.
7. Life expectancy of less than 6 months.
8. Pregnant or breast-feeding.
9. Female subject of childbearing potential without use of effective non-hormonal birth control methods or not willing to continue practicing these birth control methods for at least 30 days after the end of the treatment period.
Note: Hormonal based contraception may not be reliable when taking TMC114,
therefore to be eligible for this study women of childbearing potential should
either:
(1) use a double barrier method to prevent pregnancy (i.e., use a condom with
either diaphragm or cervical cap), or,
(2) use hormonal based contraceptives in combination with a barrier contraceptive (i.e., male condom, diaphragm or cervical cap or female condom), or,
(3) use an intra uterine device (IUD) in combination with a barrier contraceptive
(i.e., male condom, diaphragm or cervical cap or female condom), or,
(4) be non-heterosexually active, practice sexual abstinence or have a vasectomized partner (confirmed sterile).
Note: Women who are postmenopausal for at least 2 years, women with total
hysterectomy and women with tubal ligation are considered of non-childbearing
potential.
10. Subjects with clinical or laboratory evidence of significantly decreased hepatic function or decompensation (i.e. liver insufficieny), irrespective of liver enzyme levels.
Note: Subjects co-infected with chronic hepatitis B or C will be allowed to enter the trial if their condition is clinically stable and is not expected to require treatment during the study period. Subjects diagnosed with acute viral hepatitis at screening will not be allowed in the trial. Please refer to the package insert with respect to proper care of hepatitis B co-infection in case tenofovir and emtricitabine are included in the OBR.
11. Any active clinically significant disease (e.g., TB, cardiac dysfunction, pancreatitis, acute viral infections) or findings during screening of medical history or physical examination that, in the investigator’s opinion, would compromise the subjects safety or outcome of the study.
12. Subjects with a grade 3 or 4 laboratory abnormality as defined by DAIDS grading tab

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective is to demonstrate non-inferiority in virologic response, defined as a confirmed plasma viral load of less than 400 copies/mL, with TMC114/RTV 600/100 mg b.i.d. versus LPV/RTV 400/100 mg b.i.d. at 48 weeks, when administered in combination with an individually optimized background regimen (OBR).;Secondary Objective: The secondary objectives are:<br>- to evaluate safety and tolerability over 96 weeks;<br>- to evaluate the durability of efficacy over 96 weeks;<br>- to evaluate the change in viral load from baseline;<br>- to evaluate the percentage of subjects with undetectable viral load defined as viral load < 50 copies/mL);<br>- to compare the immunologic response;<br>- to compare the quality of life.;Primary end point(s): demonstration of non-inferiority in efficacy of TMC114/RTV versus lopinavir/ritonavir

Secondary Outcome Measures

Name	Time	Method