The main purpose of this study is to examine the effect of tipranavir combined with
ritonavir, medications for the treatment of HIV-infection, on buprenorphine/naloxone (BUP) in
people who have been receiving the same dose of buprenorphine/naloxone for at least 3 weeks
before study entry.
Earlier studies looking at the combination of BUP and HIV medications have shown that BUP and
some HIV medications act differently when taken together. It is important to learn if taking
BUP and HIV medications together results in changes in the blood level of either medication.
If the HIV medication decreases the level of BUP in the blood, an individual taking BUP and
HIV medications may experience symptoms of withdrawal ("dope sickness"), even while taking
their usual dose of BUP. On the other hand, if BUP decreases the amount of HIV medication in
the blood, then the HIV medication may be less effective in controlling HIV infection. It is
therefore important to learn if tipranavir/ritonavir and BUP will affect each other when
taken together.
In order to learn about the effects of BUP on tipranavir/ritonavir, we will need to measure
the amount of BUP in your blood for 24 hours after you have taken tipranavir/ritonavir and
BUP together and then compare that to the amount of BUP in your blood when you are not taking
tipranavir/ritonavir.
Inclusion Criteria:
- Buprenorphine/naloxone (BUP/NAL) users (taking 16/4 mg sublingually daily) for at
least 3 weeks deemed by the investigator to have acceptable medical history, physical
examination, 12 lead electrocardiogram, and clinical laboratory evaluations consistent
with BUP maintenance will be eligible to participate in the study.
- Subjects who meet the criteria of opiate dependence, are enrolled in long-term BUP
maintenance therapy, and have been on a stable dose of BUP/NAL for at least 3 weeks.
- Body weight > 60 kg for males and > 40 kg for females
- Body Mass Index (BMI) of 18 to 30 kg/m2, inclusive. BMI = weight (kg)/ [height(m)]2.
- Male or females, ages > 18 to < 60 years.
- Women of childbearing potential (WOCBP) must not be nursing or pregnant and must be on
adequate non-hormonal contraception to avoid pregnancy. WOCBP must have a negative
serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG)
within 24 hours prior to the start of Study Day 1.
Exclusion Criteria:
- History or current evidence of any significant acute or chronic medical illness that,
within the investigator's discretion, would interfere with the conduct or
interpretation of the study.
- History of acute or chronic pancreatitis.
- History of uncontrolled chronic medical illness which could adversely affect the
subject's adherence to study protocol or affect patient safety in the opinion of the
investigator
- Use of any medication thought to significantly alter the metabolism of tipranavir,
ritonavir, Buprenorphine or naloxone.
- History of any hemolytic disorders (including drug-induced hemolysis).
- Proven or suspected acute hepatitis at the time of study entry.
- Chronic liver disease with Childs-Pugh Class B or C staging
- Current or recent (within 3 months) gastrointestinal disease which would interfere
with the conduct or interpretation of the study.
- Any major surgery within 4 weeks of enrollment. Minor surgical procedures requiring
local anesthesia are exceptions.
- Any gastrointestinal surgery that could impact upon the absorption of study drug.
- Donation of blood or plasma to a blood bank or in a clinical study (except a screening
visit) within 4 weeks of enrollment.
- Blood transfusion within 4 weeks of enrollment.
- Inability to tolerate oral medication.
- Inability to tolerate venipuncture and/or absence of secure venous access.
- Inability to refrain from smoking during in-residence period
- Known or suspected HIV infection (subjects who are found to be positive upon screen
for HIV will be excluded).
- Known active drug or alcohol abuse, which in the opinion of the investigator makes
study participation to completion unlikely.
- Any other sound medical, psychiatric and/or social reason as determined by the
Investigator.
- Evidence of organ dysfunction or any clinically relevant (as determined by the
investigator) deviations from the norms observed in a buprenorphine/naloxone treated
population in physical examination, vital signs, ECG or clinical laboratory
determinations.
- Ingestion of alcohol within 24 hours prior to the dose of study medication
- Positive breathalyzer alcohol test, or positive urine screen for barbiturates,
benzo-diazepines, amphetamines, THC, cocaine or opiates other than
buprenorphine/naloxone.
- Positive blood screen for HIV antibody.
- Subjects with AST, ALT or bilirubin > 2. 5X the upper limit of normal.
- Hemoglobin < 9 g/dL, and platelet count < 75, 000/mm3.
- Positive serum or urine for HCG.
- History of any significant drug allergy, drug rash or sensitivity to any class of
drugs relevant to the study drugs.
