The primary objective of this study is to characterise the effects of tipranavir 500 mg and
ritonavir 200 mg (TPV/r; given twice daily) at steady-state on the pharmacokinetics of
methadone administered as a single dose in healthy adult volunteers
Inclusion Criteria:
- Male or female healthy volunteers aged at least 18 to 60 years.
- Clinically normal medical history.
- Clinically normal findings on physical examination.
- Clinically normal laboratory values.
- A Body Mass Index >18. 5 and <30 kg/m2.
- Able to swallow large capsules without difficulty.
- Capable of comprehending and communicating effectively with the investigator and
staff and of providing written informed consent in accordance with ethics committee
and regulatory guidelines.
- Willing to stay in the study centre for the duration of the study.
- Willing to abstain from ingesting substances during the study which may alter plasma
study drug levels by interaction with the cytochrome P450 system.
- Willing to abstain from alcohol for 48 hours prior to Visit 1 and for the duration of
the study. In addition, Cabernet Sauvignon must not have been ingested within 15 days
prior to Visit 1.
- Willing to abstain from ingesting grapefruit and grapefruit juice for 15 days before
Visit 1 and for the duration of the study.
- Willing to abstain from ingesting Seville oranges, strawberries or strawberry
extract, garlic supplements, St. John's Wort, Milk Thistle, or
methylxanthine-containing drinks or food (coffee, tea, cola, energy drinks,
chocolate, etc) for 72 hours before the pharmacokinetic sampling days.
- Willing to abstain from use of tobacco products for the duration of the study.
- Urine drug screen negative for illegal non-prescription drugs.
- Negative HIV serology.
- Negative for Hepatitis B surface antigen and Hepatitis C
Exclusion Criteria:
- Any clinically significant disease. (A significant disease was defined as a disease
which in the opinion of the investigator may either have put the subject at risk
because of participation in the study or a disease which may have influenced the
results of the study or the subject's ability to participate in the study.)
- Clinically significant abnormal baseline haematology, blood chemistry or urinalysis
findings.
- Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol,
triglyceride or glucose greater than the upper limit of normal at Visit 1.
- Treatment with prohibited medications in the thirty days before the study or during
the study or ingestion of drugs of abuse.
- Treatment with any investigational drug within 90 days of the first dose of study
medication.
- Inability to adhere to the requirements of the protocol (including active substance
abuse) as assessed by the investigator.
- Prior tipranavir use.
- Ingestion of any known enzyme altering drug (such as phenothiazines, cimetidine,
barbiturates, ketoconazole, fluconazole, clarithromycin, rifampin, steroids, and
herbal medications) for thirty days prior to Visit 1.
- Ingestion of grapefruit, grapefruit juice, and Cabernet Sauvignon within fifteen days
prior to Visit 1.
- Ingestion of Seville oranges, strawberries or strawberry extract, garlic supplements,
St. John's Wort, Milk Thistle, or methylxanthine-containing drinks or food (coffee,
tea, cola, energy drinks, chocolate, etc) within 72 hours of pharmacokinetics
sampling days.
- Treatment with prescription medicines within thirty days prior to Visit 1.
- History of gastrointestinal, hepatic, or renal disorders within 60 days prior to
Visit 1.
- Any history of alcohol or drug abuse.
- Current use of cigarettes defined as greater than 10 cigarettes per day or
rolling/pipe tobacco equivalent.
- Blood or plasma donations within 90 days prior to Visit 1
- Subjects with a seated systolic blood pressure either <100 mm Hg or >150 mm Hg;
resting heart rate either <50 beats/min or >100 beats/min.
- Subjects with a history of any illness or allergy that, in the opinion of the
investigator, might have confounded the results of the study or posed additional risk
in administering tipranavir, ritonavir or methadone to the subject.
- Subjects who had an acute illness within two weeks prior to Visit 1.
- Subjects who were currently taking any over-the-counter drug within fourteen days
prior to Visit 1 or who were currently taking any prescription drug.
- Hypersensitivity to tipranavir, ritonavir, or methadone.
- Female subjects who are of reproductive potential and who were pregnant,
breastfeeding, had a positive serum B-HCG at Visit 1 or 2, had not been using a
barrier contraceptive method for at least three months prior to Study Day 1 or were
not willing to use a reliable method of double-barrier contraception (such as
diaphragm with spermicidal cream/jelly or condoms with spermicidal foam) during the
study and for thirty days after completion or termination of the study.
