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

NCT01635829 | Completed Phase 1

• 3 other identifiers: CR100830VX-950HPC10022012-001411-23
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Participants

Keywords

Healthy participants; Hepatitis C virus; Telaprevir; Phenytoin; Carbamazepine; HCV; Interaction

Outcome Measures

Primary Outcomes (9)

• Observed maximum plasma concentration (Cmax) of telaprevir.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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 Outcomes (5)

• Number of participants with adverse events

  Up to Day 17

• Number of participants with abnormal values of laboratory results

  Up to Day 17

• Number of participants with abnormal electrocardiogram values

  Up to Day 17

• Number of participants with abnormal pulse and blood pressure values

  Up to Day 17

• Number of patients with abnormal physical examination findings

  Up to Day 17

Study Arms (2)

Panel 1

EXPERIMENTAL

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.

Drug: Telaprevir; Drug: Phenytoin

Panel 2

EXPERIMENTAL

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.

Drug: Telaprevir; Drug: Carbamazepine

Interventions

Telaprevir DRUG

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.

Panel 1; Panel 2

Phenytoin DRUG

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.

Panel 1

Carbamazepine DRUG

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.

Panel 2

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Infectious Diseases BVBA: lead

Study Sites (1)

Unknown Facility

Groningen, Netherlands

Location

MeSH Terms

Conditions

Hepatitis C

Interventions

telaprevir; Phenytoin; Carbamazepine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Hydantoins; Imidazolidines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Janssen Infectious Diseases BVBA Clinical Trial

  Janssen Infectious Diseases BVBA

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 4, 2012
• First Posted: July 10, 2012
• Study Start: May 1, 2012
• Primary Completion: August 1, 2012
• Study Completion: September 1, 2012
• Last Updated: October 24, 2013

Record last verified: 2013-10

Locations

NL (1)