| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10020161 |
| E.1.2 | Term | HIV infection |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| 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). |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
- to evaluate safety and tolerability over 96 weeks;
- to evaluate the durability of efficacy over 96 weeks;
- to evaluate the change in viral load from baseline;
- to evaluate the percentage of subjects with undetectable viral load defined as viral load < 50 copies/mL);
- to compare the immunologic response;
- to compare the quality of life. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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. |
|
| E.4 | Principal 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, irrespective of liver enzyme levels(liver insufficiency).
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 tables (see Section 7.5), with the following exceptions unless clinical assessment foresees an immediate health risk to the subject:
• Subjects with pre-existing diabetes or with asymptomatic glucose grade 3 or 4
elevations.
• Subjects with asymptomatic triglyceride or cholesterol elevations of grade 3 or 4.
13. Previously demonstrated clinically significant allergy or hypersensitivity to any of the excipients of the investigational medication (TMC114) LPV or RTV.
Note: TMC114 is a sulfonamide. Subjects who previously experienced a sulfonamide
allergy will be allowed to enter the trial. To date, no potential for cross sensitivity
between drugs in the sulfonamide class and TMC114 has been identified in patients
participating in phase II trials.
14. Participation in other investigational trials without prior approval of the sponsor.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| demonstration of non-inferiority in efficacy of TMC114/RTV versus lopinavir/ritonavir |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 64 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
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