A Study to Investigate the Potential Pharmacokinetic Interactions Between Phenytoin or Carbamazepine and Telaprevir

October 23, 2013 updated by: Janssen Infectious Diseases BVBA

A Phase I, Open-label, Randomized, 2-panel, Sequential Treatment Study in Healthy Subjects to Investigate the Potential Pharmacokinetic Interactions Between Multiple Doses of Phenytoin or Carbamazepine and Telaprevir at Steady-state

The purpose of this study is to investigate the potential pharmacokinetic (what the body does to the drug) interactions between multiple doses of phenytoin 200 mg every 12 hours or carbamazepine 200 mg every 12 hours and telaprevir 750 mg every 8 hours at steady-state (constant concentration of medication in the blood) in healthy participants.

Study Overview

Status

Completed

Detailed Description

This is a Phase I, open-label (all people know the identity of the intervention), randomized (the study medication is assigned by chance), 2-panel, sequential treatment study. In this study 24 healthy participants will be randomly assigned equally to 2 panels. In Panel 1 the participants will receive telaprevir in Part 1 (telaprevir 750 mg every 8 hours from Day 1 to Day 9 followed by a single 750 mg dose in the morning on Day 10) and phenytoin/telaprevir in Part 2 (phenytoin 200 mg every 12 hours from Day 1 to Day 16 followed by a single 200-mg dose in the morning on Day 17; and telaprevir 750 mg every 8 hours from Day 8 to Day 16 followed by a single 750 mg dose in the morning on Day 17). In Panel 2 the participants will receive telaprevir (telaprevir 750 mg every 8 hours from Day 1 to Day 9 followed by a single 750 mg dose in the morning on Day 10) and carbamazepine/ telaprevir (carbamazepine 200 mg every 12 hours from Day 1 to Day 16 followed by a single 200-mg dose in the morning on Day 17; and telaprevir 750 mg every 8 hours from Day 8 to Day 16 followed by a single 200-mg dose in the morning on Day 17). In both panels, Part 1 and Part 2 are separated by a washout period of at least 2 weeks and maximum 4 weeks. Safety and tolerability will be assessed by evaluating adverse events, electrocardiogram, clinical laboratory examinations, vital signs and physical examination throughout the study period.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Must be healthy on the basis of physical examination, medical history, vital signs, clinical laboratory tests, and electrocardiogram performed at screening
  • If a woman, before entry she must be postmenopausal for at least 2 years (amenorrheal for at least 3 years), or surgically sterile (have had a total hysterectomy or bilateral oophorectomy, tubal ligation/bilateral tubal clips without reversal operation, or otherwise be incapable of becoming pregnant)
  • Men must agree to use a highly effective method of birth control (ie, male condom with either female intrauterine device [IUD], diaphragm, cervical cap or hormone based contraceptives by their female partner) and to not donate sperm during the study and for 3 months after receiving the last dose of study drug
  • A 12-lead electrocardiogram consistent with normal cardiac conduction and function

Exclusion Criteria:

  • Participants with a history of any illness that, in the opinion of the Investigator or the participant's general practitioner, might confound the results of the study or pose an additional risk in administering study drug(s) to the participant
  • Participants of Asian ancestry (given association of phenytoin / carbamazepine and severe rash with HLA-B 1502 in this population)
  • Current use of prescription medication, and regular use or routine use of concomitant medication(s), including over-the-counter (OTC) products
  • Consumption of herbal medications or dietary supplements (eg, St. John's Wort, Ginkgo biloba, garlic supplements), vitamins, and grapefruit or grapefruit juice, apple juice, or orange juice within 14 days before the first administration of study drug
  • Consumption of an average of more than five 240-mL servings of coffee or other caffeinated beverage per day

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Panel 1
Part 1 of Panel 1: Participants will receive telaprevir 750 mg every 8 hours from Day 1 to Day 9 followed by a single 750-mg dose in the morning on Day 10. Part 2 of Panel 1: Participants will receive phenytoin 200 mg every 12 hours from Day 1 to Day 16 followed by a single 200-mg dose in the morning on Day 17; and telaprevir 750 mg every 8 hours from Day 8 to Day 16 followed by a single 750-mg dose in the morning on Day 17.
Type=exact number, unit=mg, number=375, form=tablet, route=oral. Two tablets of telaprevir will be administered as per the dosing regimens for each part of both the panels.
Type=exact number, unit=mg, number=100, form=capsule, route=oral. Two capsules of phenytoin will be administered as per the dosing regimen in Part 2 of Panel 1.
Experimental: Panel 2

Part 1 of Panel 2: Participants will receive telaprevir 750 mg every 8 hours from Day 1 to Day 9 followed by a single 750-mg dose in the morning on Day 10. Part 2 of Panel 2: Participants will receive carbamazepine 200 mg every 12 hours from Day 1 to Day 16 followed by a single 200-mg dose in the morning on Day 17; and telaprevir 750 mg every 8 hours from Day 8 to Day 16 followed by a single 750-mg dose in the morning on Day 17.

brief description of the arm. This element may not be necessary if the associated intervention descriptions contain sufficient information to describe the arm.

Type=exact number, unit=mg, number=375, form=tablet, route=oral. Two tablets of telaprevir will be administered as per the dosing regimens for each part of both the panels.
Type=exact number, unit=mg, number=200, form=tablet, route=oral. One tablet of carbamazepine will be administered as per dosing regimen in Part 2 of Panel 2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Observed maximum plasma concentration (Cmax) of telaprevir.
Time Frame: Part 1: predose (Day 1, 8, 9 , and 10) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, and 8h(Day 1 and Day 10); Part 2: predose (Day 1, 2, 6, 7, 8, 9, 10, 15, 16, and 17) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (Day 7, 8, and 17)
Part 1: predose (Day 1, 8, 9 , and 10) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, and 8h(Day 1 and Day 10); Part 2: predose (Day 1, 2, 6, 7, 8, 9, 10, 15, 16, and 17) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (Day 7, 8, and 17)
Area under the plasma concentration time curve from time of administration up to 8 hours post dose (AUC8h) of telaprevir.
Time Frame: Part 1: predose (Day 1, 8, 9 , and 10) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, and 8h(Day 1 and Day 10); Part 2: predose (Day 1, 2, 6, 7, 8, 9, 10, 15, 16, and 17) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (Day 7, 8, and 17)
Part 1: predose (Day 1, 8, 9 , and 10) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, and 8h(Day 1 and Day 10); Part 2: predose (Day 1, 2, 6, 7, 8, 9, 10, 15, 16, and 17) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (Day 7, 8, and 17)
Observed minimum plasma concentration (Cmin) of telaprevir.
Time Frame: Part 1: predose (Day 1, 8, 9 , and 10) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, and 8h(Day 1 and Day 10); Part 2: predose (Day 1, 2, 6, 7, 8, 9, 10, 15, 16, and 17) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (Day 7, 8, and 17)
Part 1: predose (Day 1, 8, 9 , and 10) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, and 8h(Day 1 and Day 10); Part 2: predose (Day 1, 2, 6, 7, 8, 9, 10, 15, 16, and 17) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (Day 7, 8, and 17)
Observed maximum plasma concentration (Cmax) of carbamazepine.
Time Frame: Part 1: predose (Day 1, 8, 9 , and 10) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, and 8h(Day 1 and Day 10); Part 2: predose (Day 1, 2, 6, 7, 8, 9, 10, 15, 16, and 17) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (Day 7, 8, and 17)
Part 1: predose (Day 1, 8, 9 , and 10) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, and 8h(Day 1 and Day 10); Part 2: predose (Day 1, 2, 6, 7, 8, 9, 10, 15, 16, and 17) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (Day 7, 8, and 17)
Area under the plasma concentration time curve from time of administration up to 12 hours post dose (AUC12) of carbamazepine.
Time Frame: Part 1: predose (Day 1, 8, 9 , and 10) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, and 8h(Day 1 and Day 10); Part 2: predose (Day 1, 2, 6, 7, 8, 9, 10, 15, 16, and 17) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (Day 7, 8, and 17)
Part 1: predose (Day 1, 8, 9 , and 10) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, and 8h(Day 1 and Day 10); Part 2: predose (Day 1, 2, 6, 7, 8, 9, 10, 15, 16, and 17) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (Day 7, 8, and 17)
Observed minimum plasma concentration (Cmin) of carbamazepine.
Time Frame: Part 1: predose (Day 1, 8, 9 , and 10) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, and 8h(Day 1 and Day 10); Part 2: predose (Day 1, 2, 6, 7, 8, 9, 10, 15, 16, and 17) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (Day 7, 8, and 17)
Part 1: predose (Day 1, 8, 9 , and 10) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, and 8h(Day 1 and Day 10); Part 2: predose (Day 1, 2, 6, 7, 8, 9, 10, 15, 16, and 17) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (Day 7, 8, and 17)
Observed maximum plasma concentration (Cmax) of phenytoin.
Time Frame: Part 1: predose (Day 1, 8, 9 , and 10) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, and 8h(Day 1 and Day 10); Part 2: predose (Day 1, 2, 6, 7, 8, 9, 10, 15, 16, and 17) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (Day 7, 8, and 17)
Part 1: predose (Day 1, 8, 9 , and 10) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, and 8h(Day 1 and Day 10); Part 2: predose (Day 1, 2, 6, 7, 8, 9, 10, 15, 16, and 17) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (Day 7, 8, and 17)
Area under the plasma concentration time curve from time of administration up to 12 hours post dose (AUC12) of phenytoin.
Time Frame: Part 1: predose (Day 1, 8, 9 , and 10) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, and 8h(Day 1 and Day 10); Part 2: predose (Day 1, 2, 6, 7, 8, 9, 10, 15, 16, and 17) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (Day 7, 8, and 17)
Part 1: predose (Day 1, 8, 9 , and 10) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, and 8h(Day 1 and Day 10); Part 2: predose (Day 1, 2, 6, 7, 8, 9, 10, 15, 16, and 17) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (Day 7, 8, and 17)
Observed minimum plasma concentration (Cmin) of phenytoin.
Time Frame: Part 1: predose (Day 1, 8, 9 , and 10) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, and 8h(Day 1 and Day 10); Part 2: predose (Day 1, 2, 6, 7, 8, 9, 10, 15, 16, and 17) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (Day 7, 8, and 17)
Part 1: predose (Day 1, 8, 9 , and 10) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, and 8h(Day 1 and Day 10); Part 2: predose (Day 1, 2, 6, 7, 8, 9, 10, 15, 16, and 17) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (Day 7, 8, and 17)

Secondary Outcome Measures

Outcome Measure
Time Frame
Number of participants with adverse events
Time Frame: Up to Day 17
Up to Day 17
Number of participants with abnormal values of laboratory results
Time Frame: Up to Day 17
Up to Day 17
Number of participants with abnormal electrocardiogram values
Time Frame: Up to Day 17
Up to Day 17
Number of participants with abnormal pulse and blood pressure values
Time Frame: Up to Day 17
Up to Day 17
Number of patients with abnormal physical examination findings
Time Frame: Up to Day 17
Up to Day 17

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2012

Primary Completion (Actual)

August 1, 2012

Study Completion (Actual)

September 1, 2012

Study Registration Dates

First Submitted

July 4, 2012

First Submitted That Met QC Criteria

July 4, 2012

First Posted (Estimate)

July 10, 2012

Study Record Updates

Last Update Posted (Estimate)

October 24, 2013

Last Update Submitted That Met QC Criteria

October 23, 2013

Last Verified

October 1, 2013

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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