Effects of TPV/r on the Pharmacokinetics of Carbamazepine in Healthy Adult Volunteers

A Single Centre, Open-label Study With Healthy Adult Volunteers to Determine the Effects of Single-dose and Steady-state TPV/r 500/200 mg on the Steady-state Pharmacokinetics of Carbamazepine (200 mg Twice Daily)

Study to assess the steady-state pharmacokinetics of carbamazepine (CBZ) at 200 mg or 100 mg twice daily, depending on tolerability, and administered alone and in combination with tipranavir/ritonavir (TPV/r) after a single dose (500/200 mg) and at steady-state (500/200 mg twice-daily)

Inclusion Criteria:

• Healthy male and non-pregnant, non-lactating female subjects as determined by results of screening
• Signed written informed consent in accordance with Good Clinical Practice (GCP) and local legislation
• 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 study requirements
• Age >19 and <59 years
• Weight ≥ 60 kg
• BMI >18.5 and <35 kg/m2
• Ability to maintain adequate contraception if applicable

Exclusion Criteria:

• Any finding of the medical examination (including blood pressure, pulse rate, and electrocardiogram) deviating from normal and of clinical relevance
• AV block including 1°
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, haematological, oncological or hormonal disorders
• Surgery of gastrointestinal tract (except appendectomy)
• Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
• Relevant history of orthostatic hypotension, fainting spells or blackouts
• Chronic or relevant acute infections
• History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
• Known hypersensitivity to TPV, Ritonavir (RTV), carbamazepine or antiretroviral drugs (marketed or experimental use as part of clinical research studies)
• Known elevated liver enzymes in past trials with any compound
• Intake of drugs with a long half-life (>24 hours) (<1 month prior to administration or during the trial)
• Prescription or over the counter medications (including vitamins, minerals, herbal supplements and antacids), dietary supplements 14 days prior to study drug administration or expected during the trial)
• Participation in another trial with an investigational drug (<2 months prior to administration or expected during trial)
• Smoker with a consumption of >10 cigarettes or >3 cigars or >3 pipes/day and those who cannot keep tobacco intake constant
• Alcohol abuse (>60 g/day)
• Drug abuse
• Blood donation or loss >400 mL, <1 month prior to administration or expected during the trial
• Clinically relevant laboratory abnormalities
• Inability to comply with dietary regimen of study centre

For female subjects:

• Pregnancy or planning to become pregnant within 60 days of study completion
• Positive pregnancy test
• Have not been using a barrier method of contraception for at least 3 months prior to participation in the study
• Are not willing or are unable to use a reliable method of barrier contraception (such as diaphragm with spermicidal cream/jelly or condoms with spermicidal foam), during and up to 2 months after completion/termination of the trial
• Chronic use of oral contraception or hormone replacement containing ethinyl estradiol
• Breast-feeding