A Phase IIb randomized, partially blinded, dose-finding trial ofTMC278 in antiretroviral naive HIV-1 infected subjects. - N/A

• Conditions: HIV infection; MedDRA version: 12.1Level: LLTClassification code 10020161Term: HIV infection

• Registration Number: EUCTR2004-004055-19-DE
• Lead Sponsor: Tibotec Pharmaceuticals

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-03-17
• Last Update Posted: 7 January 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 368

Inclusion Criteria

Subjects who meet all of the following criteria are eligible for this trial:
1. Male or female subjects, aged 18 years or above.
2. Subject having documented HIV-1 infection.
3. Subject is willing to sign the informed consent form voluntarily.
4. Cortisol of at least 550 nmol/L (19.9 µg/dL) at least at one of the 3 timepoints (i.e., morning cortisol, 30 or 60 minutes after 250 µg ACTH stimulation) on the screening assessment.
5. Subject can comply with the protocol requirements.
6. HIV-1 plasma viral load at screening visit above 5000 HIV-1 RNA copies/mL (assayed by RNA polymerase chain reaction standard specimen procedure).
7. In the judgement of the investigator, it is appropriate to initiate ARV therapy based on the
subject's clinical condition and taking into account guidelines for the treatment of HIV-1 infection.
8. Subject has never been treated with an ARV drug or therapeutic HIV vaccine, or has received = 2 weeks treatment prior to screening with an NRTI and/or PI.
9. Screening virco®TYPE HIV-1 demonstrates sensitivity to investigator selected nucleosides.
10. Subject agrees not to start ARV before the baseline visit.
11. General medical condition, in the investigator’s opinion, does not interfere with the assessments and the completion of the trial.

Criteria for Entering the Optional Open-Label Extention Part I, II:
1. The subject has completed the entire 96-week treatment period and has voluntarily agreed to participate (i.e., has signed the updated ICF).
2. The subject has completed the entire 144-week treatment period and has voluntarily agreed to participate (i.e., has signed the updated ICF).
3. The subject is willing to comply with the protocol requirements and cooperate with the investigator.

Criteria for Entering the Optional Open-Label Extension Part III:
1. The subject has completed the entire 240-week treatment period with TMC278 and has voluntarily agreed to
participate (i.e., has signed the updated ICF).
2. The subject continues to benefit from this treatment.
3. The subject lives in a region where TMC278 is not yet commercially available, reimbursed by the public and/
or private health system or cannot be accessed from another source (e.g., access program, government program).
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. Use of disallowed conc. therapy
2. History of or currently active alcohol or drug use which will likely compromise subjects’ safety and/or compliance with trial procedures.
3. Life expectancy less than 6 months.
4. Subject has any currently active AIDS defining illness with the following exception:
- Stable, cutaneous Kaposi Sarcoma that is unlikely to require any form of systemic therapy during the trial period;
- Wasting syndrome due to HIV infection if it is not actively progressive and its treatment does not require hospitalization or compromise the subject’s safety or compliance to adhere to the trial protocol procedures.
5. Any active clinically significant disease or findings during screening of medical history or physical examination that, in the investigator’s opinion, would compromise the outcome of the trial.
6. Subject has known or suspected acute (primary) HIV-1 infection.
7. Any use of NNRTIs.
8. Acute hepatitis A, B, or C infection.
9. Having documented genotypic evidence of NNRTI resistance at screening or from historical data available in the source documents.
A098G
L100I
K101E
K101P
K101Q
K103H
K103N
K103S
K103T
V106A
V106M
V108I
Y181C
Y181I
Y181V
Y188C
Y188H
Y188L
G190A
G190E
G190S
P225H
M230L
P236L
K238N
K238T
Y318F
10. Any current or history of adrenal disorder.
11. Receipt of any investigational drug within 90 days prior to the trial drug administration.
12. Previously demonstrated clinically significant allergy or hypersensitivity to any of the
components of the investigational medication.
13. Pregnant or breastfeeding female.
14. Female of childbearing potential without the use of effective birth control methods or not willing to continue practicing these birth control methods during the trial and until 14 days after the end of the trial (or after last intake of ARVs).
Note: Hormonal based contraception may not be reliable when taking TMC278, therefore to be eligible for this trial, women of childbearing potential should either:
1) use a double barrier method to prevent pregnancy;
OR
2) use hormonal based contraceptive in combination with a barrier contraceptive;
OR
3) use an intrauterine device in combination with a barrier contraceptive;
OR
4) be non-heterosexually active, practice sexual abstinence or have a vasectomized partner.
Note: Women who are postmenopausal for at least 2 years, women with total
hysterectomy and women who have had a tubal ligation are considered of nonchildbearing potential.
15. Heterosexually active males without the use of effective birth control methods or not willing to continue practicing these birth control methods during the trial and until 30 days after the end of the trial (or after last intake of ARVs). All HIV-infected male subjects are advised to use a condom to reduce the risk of transmitting HIV. Since the effects of TMC278 on conception are unknown, non-vasectomized heterosexual male subjects are advised to use one of the following birth control methods:
- a condom with spermicide, or
- a condom or a spermicide combined with either hormonal contraceptives, IUD,
diaphragm, cervical cap or female condom, or
- refrain from heterosexual intercourse
from screening onwards until one month after the last study drug administration i.e., until the 30-days follow-up visit or one month after discontinuation of the study medication in case of premature discontinuation.
The use of the above mentioned birth control methods does not apply if the male HIVinfected subject has been

Study & Design

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