This study is being conducted to look at how the body handles the drugs darunavir and
etravirine. It will measure the amount of darunavir and etravirine in blood, semen, and in
the rectum of men. The aim is to understand how much of the drug (taken by mouth) reaches
the reproductive and intestinal tracts. It is believed that the presence of this drug in
these areas may be beneficial in preventing the AIDS virus (HIV) from being passed from one
person to another. The study will take samples of blood, semen and rectal mucosal tissue to
measure drug levels. This study will also collect information on side effects.
Inclusion Criteria:
- Healthy male subjects between the ages of 18 and 49 years, inclusive, with intact
genital tract and gastrointestinal tract. (Healthy is defined as no clinically
relevant abnormalities identified by a detailed medical history, full physical
examination, including blood pressure and pulse rate measurement, 12-lead ECG for
individuals >35yo and clinical laboratory tests).
- Body Mass Index (BMI) of approximately 18 to 30 kg/m2; and a total body weight >/=50
kg (110 lbs).
- Evidence of a personally signed and dated informed consent document indicating that
the subject has been informed of all pertinent aspects of the trial.
- Willing and able to comply with scheduled visits, treatment plan, laboratory tests,
and other trial procedures.
Exclusion Criteria:
- Evidence or history of clinically significant hematological, renal, endocrine,
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or
allergic disease (including drug allergies, but excluding untreated, asymptomatic,
seasonal allergies at time of dosing).
- Subjects with a history of having a gastrectomy, colostomy, ileostomy, or any other
procedure altering the gastrointestinal tract.
- Subjects with inflammatory bowel diseases (ulcerative colitis or Crohn's disease) and
have a clearly defined diagnosis of irritable bowel syndrome.
- Subject who is unwilling to refrain from any sexual activity including intercourse
and masturbation for 72 hours prior study visit Day 1 and until discharge from the
study.
- Subject who is unwilling to refrain from rectal insertion of medical/recreation
devices and products and from receptive anal intercourse, for 72 hours before study
visit Day - 1 and through 7 days after the last biopsy unless instructed otherwise by
the investigators.
- History of febrile illness within 5 days prior to the first dose.
- Any condition possibly affecting drug absorption (eg, gastrectomy).
- A positive urine drug screen.
- A positive result for HIV.
- Active hepatitis B infection as defined by a positive Hepatitis B surface antigen
(HbsAg) OR a positive Hepatitis B core antibody with a negative Hepatitis B surface
antibody (HBsAb).
- Active hepatitis C infection as defined by anti-hepatitis C virus serology (as
determined by multi-antigen EIA) and detectable HCV RNA.
- A positive test for syphilis, gonorrhea, Chlamydia, HSV-2 (active lesions) or
trichomonas at screening.
- History of regular alcohol consumption exceeding 14 drinks (1 drink = 5 ounces (150
mL) of wine or 12 ounces (360 mL) of beer or 1. 5 ounces (45 mL) of spirits) per week.
- Participation in a clinical study within 4 months preceding the first dose of trial
medication.
- Participation in a rectal biopsy study in the 12 months preceding the first dose of
trial medication.
- Use of prescription or nonprescription drugs, vitamins and dietary supplements within
7 days or 5 half-lives (whichever is longer) prior to the first dose of trial
medication. Herbal supplements must be discontinued 14 days prior to the first dose
of trial medication. As an exception, acetaminophen may be used at doses of - Blood donation of approximately 1 pint (500 mL) within 56 days prior to dosing.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
- Unwilling to abstain from alcohol use from 24 hours prior to the first dose of study
medication until after the follow-up visit.
- Unwilling to abstain from cigarette smoking completely during inpatient
pharmacokinetic visits and unwilling to limit smoking to a maximum of 5 cigarettes
per day from 24 hours prior to the start of the study until study completion.
- Unwilling or unable to comply with the dietary restrictions in regard to study drug
administration
