Study in Healthy Volunteers of the Safety and Metabolism of Different Doses of the Anti-HIV Drug TMC278LA.

This is an interventional prevention trial for HIV Infection focused on measuring HIV Read More

Inclusion Criteria:

1. The ability to understand and sign a written informed consent form, prior to participation in any screening procedures and must be willing to comply with all trial requirements.
2. Non-pregnant, non-lactating females (at least 40% will be of self-identified African ancestry)
3. Age between 18 to 50 years, inclusive.
4. Body Mass Index (BMI) of 16 to 35 kg/m2, inclusive.
5. Negative antibody/antigen combined test for HIV1 and HIV2.
6. Absence of any significant health problems (in the opinion of the investigator) on the basis of the screening procedures; including medical history, physical examination, vital signs, ECG.
7. Willing to undergo HIV testing, HIV discussion and receive HIV test results throughout the trial (according to the "UK National Guidelines for HIV Testing 2008", www.bhiva.org).
8. Women of childbearing potential (WOCBP) must be using an adequate method of contraception (intrauterine device, condoms, anatomical sterility in self or partner) to avoid pregnancy throughout the trial and for a period of at least four months after the trial follow up visit (oral hormonal methods and implant contraceptives are allowed but only in combination with the additional protection of a barrier method). Males participating in sexual intercourse that could result in pregnancy must use condoms during the duration of the study and for up to four months following the follow up visit.
9. Willing to abstain from sexual intercourse (vaginal for females and receptive anal for males) for 48 hours prior to each trial visit (with complete abstinence in the first 28 days post-dose).
10. Females willing to refrain from the use of vaginal products or objects including, tampons, female condoms, cotton wool, rags, diaphragms, cervical caps (or any other vaginal barrier method), douches, lubricants, vibrators/dildos, and drying agents for 14 days prior to enrolment and for the duration of the trial. Males willing to refrain from the use of anal products or objects including douches, lubricants and vibrators/dildos for 14 days prior to enrolment and for the duration of the trial.
11. Likely to remain resident in the UK for the duration of the trial period.
12. Willing to consent to their personal details being entered onto The Over volunteering Prevention Scheme (TOPS) database.
13. Willing to provide photographic identification at each visit.
14. Registered with a GP in the UK

Exclusion Criteria:

1. Any significant acute or chronic medical illness.
2. Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations.
3. Positive blood screen for syphilis, hepatitis A (IgM) B (HBs Ag) and/or C antibodies.
4. Positive blood screen for HIV-1 and/or HIV-2 antibodies.
5. Positive screen for sexually transmitted infections at screening visit (if bacterial vaginosis or candidiasis detected at screen, these may be treated with test-of-cure prior to enrolment).
6. Prolonged QT interval on screening ECG, or clinically significant change as judged by investigator.

7. High-risk behaviour for HIV infection which is defined as having one of the following within six months before trial day 0 (first dose):

   i. had unprotected vaginal or anal sex with a known HIV infected person or a casual partner.

   ii. engaged in sex work for money or drugs. iii. acquired a sexually transmitted disease. iv. having a high risk partner either currently or in the previous six months

8. Clinically relevant alcohol or drug use (positive urine drug screen) or history of alcohol or drug use considered by the Investigator to be sufficient to hinder compliance with treatment, follow-up procedures or evaluation of adverse events.
9. Exposure to any investigational drug or placebo within 30 days of first dose of trial drug (additional check to be made on TOPS www.tops.org.uk).
10. History of severe drug allergy that in the opinion of the Investigator may increase the risk of developing an allergic reaction to the trial drug.
11. Use of any drug, including over-the-counter medications and herbal preparations, within two weeks prior to first dose of trial drug (unless approved or prescribed by the Investigator (for exceptions see section 5.2).
12. Females who are pregnant or breast-feeding..
13. Clinically significant laboratory abnormalities (according to normal range as defined by central laboratory).