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

• ClinicalTrials.gov Identifier: NCT01635829
• Recruitment Status: Completed
• First Posted: July 10, 2012
• Last Update Posted: October 24, 2013
• Sponsor: Janssen Infectious Diseases BVBA
• Information provided by (Responsible Party): Janssen Infectious Diseases BVBA

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Healthy Participants	Drug: Telaprevir; Drug: Phenytoin; Drug: Carbamazepine	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Study Start Date: May 2012
• Actual Primary Completion Date: August 2012
• Actual Study Completion Date: September 2012

Arms and Interventions

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.	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.; Drug: 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.
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.	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.; Drug: 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.

Outcome Measures

Primary Outcome Measures :

1. 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) ]
2. 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) ]
3. 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) ]
4. 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) ]
5. 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) ]
6. 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) ]
7. 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) ]
8. 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) ]
9. 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) ]

Secondary Outcome Measures :

1. Number of participants with adverse events [ Time Frame: Up to Day 17 ]
2. Number of participants with abnormal values of laboratory results [ Time Frame: Up to Day 17 ]
3. Number of participants with abnormal electrocardiogram values [ Time Frame: Up to Day 17 ]
4. Number of participants with abnormal pulse and blood pressure values [ Time Frame: Up to Day 17 ]
5. Number of patients with abnormal physical examination findings [ Time Frame: Up to Day 17 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

Netherlands

Groningen, Netherlands

Sponsors and Collaborators

Janssen Infectious Diseases BVBA

Investigators

• Study Director: Janssen Infectious Diseases BVBA Clinical Trial; Janssen Infectious Diseases BVBA

More Information

• Responsible Party: Janssen Infectious Diseases BVBA
• ClinicalTrials.gov Identifier: NCT01635829 History of Changes
• Other Study ID Numbers: CR100830; VX-950HPC1002 ( Other Identifier: Janssen Infectious Diseases BVBA ); 2012-001411-23 ( EudraCT Number )
• First Posted: July 10, 2012
• Last Update Posted: October 24, 2013
• Last Verified: October 2013

Keywords provided by Janssen Infectious Diseases BVBA:

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

Additional relevant MeSH terms:

Carbamazepine; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP1A2 Inducers; Phenytoin; Anticonvulsants; Antimanic Agents; Tranquilizing Agents; Central Nervous System Depressants; Physiological Effects of Drugs; Psychotropic Drugs; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Sodium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Voltage-Gated Sodium Channel Blockers