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

Healthy Participants Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01635829
• Other study ID #: CR100830
• Secondary ID: VX-950HPC1002201
• Status: Completed
• Phase: Phase 1
• First received: July 4, 2012
• Last updated: October 23, 2013
• Start date: May 2012
• Est. completion date: September 2012

Study information

• Verified date: October 2013
• Source: Janssen Infectious Diseases BVBA
• Contact: n/a
• Is FDA regulated: No
• Health authority: The Netherlands: Centrale Commissie Mensgebonden Onderzoek (CCMO)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: September 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy Participants

Intervention

Drug:
• Telaprevir
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.
• Phenytoin
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.
• Carbamazepine
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Infectious Diseases BVBA

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Primary	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)	No
Primary	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)	No
Primary	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)	No
Primary	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)	No
Primary	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)	No
Primary	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)	No
Primary	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)	No
Primary	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)	No
Secondary	Number of participants with adverse events		Up to Day 17	Yes
Secondary	Number of participants with abnormal values of laboratory results		Up to Day 17	Yes
Secondary	Number of participants with abnormal electrocardiogram values		Up to Day 17	Yes
Secondary	Number of participants with abnormal pulse and blood pressure values		Up to Day 17	Yes
Secondary	Number of patients with abnormal physical examination findings		Up to Day 17	Yes