Healthy
Conditions
Brief summary
Assessment of the interaction of tipranavir/ritonavir (TPV/RTV) and valaciclovir (VAL), a prodrug of aciclovir (ACV)
Interventions
Sponsors
Boehringer Ingelheim
Study design
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 58 Years
Healthy volunteers
Yes
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 willingness to comply with all study requirements * Age \>19 and \<59 years (20 - 58 years inclusive) * Weight ≥ 60 kg * Body mass index (BMI) \>18.5 and \<29.9 kg/m2
Exclusion criteria
* Any finding of the medical examination (including blood pressure, pulse rate, and electrocardiogram) deviating from normal and of clinical relevance * Atrioventricular (AV) block including 1° * Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, hematological, 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, RTV, valaciclovir, aciclovir 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) * 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 (\>40 g/day for males and \>20 g/day for females) and drug abuse * Blood donation or loss \>400 mL, \< 3 month prior to administration * Clinically relevant laboratory abnormalities * Transaminases above reference values in the history * 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 if of childbearing potential and not surgically sterilized * 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 if of childbearing potential and not surgically sterilized * Chronic use of oral contraception or hormone replacement containing ethinyl estradiol * Breast-feeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area under the concentration-time curve of aciclovir in plasma over the time interval t0h to t12h (AUC0-12) | up to 12 hours after drug administration |
| Maximum measured concentration of aciclovir in plasma (Cmax) | up to 12 hours after drug administration |
Secondary
| Measure | Time frame |
|---|---|
| Drug concentration of TPV in plasma at 12 hours after administration (C12h) | up to 12 hours after drug administration |
| Apparent clearance of the analyte in the plasma after extravascular administration (CL/F) | up to 12 hours after drug administration |
| Apparent volume of distribution during the terminal phase λz following an extravascular dose (Vz/F) | up to 12 hours after drug administration |
| Terminal half-life of the analyte in plasma (t1/2) | up to 12 hours after drug administration |
| AUC0-12 for Tipranavir (TPV) | up to 12 hours after drug administration |
| Number of subjects with clinically significant findings in laboratory tests | up to 14 days after last drug administration |
| AUC0-12 for Ritonavir (RTV) | up to 12 hours after drug administration |
| Cmax for RTV | up to 12 hours after drug administration |
| Drug concentration of RTV in plasma at 12 hours after administration (C12h) | up to 12 hours after drug administration |
| Number of subjects with adverse events | up to 14 days after last drug administration |
| Cmax for TPV | up to 12 hours after drug administration |
Outcome results
None listed