Clinical trial NCT02226978: Pharmacokinetic Interaction Study of Steady-state Tipranavir/Ritonavir (TPV/r) With Single-dose Valaciclovir (VAL) in Healthy Volunteers
Official title: An Open-label One-sequence Cross-over Pharmacokinetic Interaction Study of Steady-state Tipranavir/Ritonavir 500/200 mg With Single-dose Valaciclovir (500 mg) in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-08-27
Enrollment: 29
Sex: ALL
Minimum age (years): 20
Maximum age (years): 58
Standard ages: ADULT
Accepts healthy volunteers: yes
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Assessment of the interaction of tipranavir/ritonavir (TPV/RTV) and valaciclovir (VAL), a prodrug of aciclovir (ACV)


Eligibility criteria: 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

Primary outcomes:
measure: Area under the concentration-time curve of aciclovir in plasma over the time interval t0h to t12h (AUC0-12)
timeFrame: up to 12 hours after drug administration
measure: Maximum measured concentration of aciclovir in plasma (Cmax)
timeFrame: up to 12 hours after drug administration
Secondary outcomes:
measure: AUC0-12 for Tipranavir (TPV)
timeFrame: up to 12 hours after drug administration
measure: Cmax for TPV
timeFrame: up to 12 hours after drug administration
measure: Drug concentration of TPV in plasma at 12 hours after administration (C12h)
timeFrame: up to 12 hours after drug administration
measure: Apparent clearance of the analyte in the plasma after extravascular administration (CL/F)
timeFrame: up to 12 hours after drug administration
measure: Apparent volume of distribution during the terminal phase λz following an extravascular dose (Vz/F)
timeFrame: up to 12 hours after drug administration
measure: Terminal half-life of the analyte in plasma (t1/2)
timeFrame: up to 12 hours after drug administration
measure: Number of subjects with adverse events
timeFrame: up to 14 days after last drug administration
measure: Number of subjects with clinically significant findings in laboratory tests
timeFrame: up to 14 days after last drug administration
measure: AUC0-12 for Ritonavir (RTV)
timeFrame: up to 12 hours after drug administration
measure: Cmax for RTV
timeFrame: up to 12 hours after drug administration
measure: Drug concentration of RTV in plasma at 12 hours after administration (C12h)
timeFrame: up to 12 hours after drug administration
Other outcomes:
Locations:
Study officials:
References: