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

Study Overview
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Brief Summary
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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)

Official Title
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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)

Conditions
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Healthy

Intervention / Treatment
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* Drug: Carbamazepine
* Drug: Tipranavir
* Drug: Ritonavir


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 58 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CBZ - TPB/r+CBZ<br>Days 1-14: carbamazepine (CBZ) twice daily Days 15-22: CBZ twice daily plus TPV/r twice daily | Drug: Carbamazepine<br> <br> Drug: Tipranavir<br> <br> Drug: Ritonavir<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve of Carbamazepine in plasma over the time interval t0h to t12h (AUC0-12h) |  | up to 12 hours after drug administration | 
| Maximum measured concentration of Carbamazepine in plasma (Cmax) |  | up to 12 hours after drug administration | 
| Drug concentration of Carbamazepine in plasma at 12 hours after drug administration (Cp12h) |  | up to 12 hours after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-12h |  | up to 12 hours after drug administration | 
| Cmax |  | up to 12 hours | 
| Cp12h |  | up to 12 hours after drug administration | 
| Clearance (CL/F) |  | up to 12 hours after drug administration | 
| Volume of distribution |  | up to 12 hours after drug administration | 
| Time from dosing to the maximum concentration (Tmax) |  | up to 12 hours after drug administration | 
| t1/2 (terminal elimination half-life) |  | up to 12 hours after drug administration | 
| Number of subjects with adverse events |  | up to 35 days | 
| Number of subjects with clinically relevant changes in laboratory parameters |  | up to 35 days |