Clinical trial NCT02253849: Effects of TPV/r on the Pharmacokinetics of Carbamazepine in Healthy Adult Volunteers
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-10-01
Enrollment: 28
Sex: ALL
Minimum age (years): 20
Maximum age (years): 58
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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)


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 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

Primary outcomes:
measure: Area under the concentration-time curve of Carbamazepine in plasma over the time interval t0h to t12h (AUC0-12h)
timeFrame: up to 12 hours after drug administration
measure: Maximum measured concentration of Carbamazepine in plasma (Cmax)
timeFrame: up to 12 hours after drug administration
measure: Drug concentration of Carbamazepine in plasma at 12 hours after drug administration (Cp12h)
timeFrame: up to 12 hours after drug administration
Secondary outcomes:
measure: AUC0-12h
timeFrame: up to 12 hours after drug administration
measure: Cmax
timeFrame: up to 12 hours
measure: Cp12h
timeFrame: up to 12 hours after drug administration
measure: Clearance (CL/F)
timeFrame: up to 12 hours after drug administration
measure: Volume of distribution
timeFrame: up to 12 hours after drug administration
measure: Time from dosing to the maximum concentration (Tmax)
timeFrame: up to 12 hours after drug administration
measure: t1/2 (terminal elimination half-life)
timeFrame: up to 12 hours after drug administration
measure: Number of subjects with adverse events
timeFrame: up to 35 days
measure: Number of subjects with clinically relevant changes in laboratory parameters
timeFrame: up to 35 days
Other outcomes:
Locations:
Study officials:
References: