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)

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Tipranavir; Drug: Ritonavir; Drug: Carbamazepine

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (Actual): June 1, 2006

Study Registration Dates

• First Submitted: September 30, 2014
• First Submitted That Met QC Criteria: September 30, 2014
• First Posted (Estimate): October 1, 2014

Study Record Updates

• Last Update Posted (Estimate): October 1, 2014
• Last Update Submitted That Met QC Criteria: September 30, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Protease Inhibitors; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Anticonvulsants; Sodium Channel Blockers; Antimanic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Tipranavir; Carbamazepine
• Other Study ID Numbers: 1182.80