Pharmacokinetics of Tasimelteon Alone and in Combination With a CYP3A4 Inhibitor, Ketoconazole, or a CYP3A4 Inducer, Rifampin.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Vanda Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01637636
First received: June 28, 2012
Last updated: February 14, 2014
Last verified: February 2014
  Purpose

The purpose of this research study is to understand whether there is any difference in the amount of tasimelteon (including its breakdown product) in the blood when taken alone and in combination with either rifampin or ketoconazole.

Cytochrome P450 3A4 is an important enzyme produced by the body to breakdown certain medications. In this study, the effect that this important enzyme has on tasimelteon is being studied by assessing the effect rifampin and ketoconazole have on tasimelteon and how they are broken down by your body. Rifampin is a known inducer of Cytochrome P450 3A4 enzyme meaning that it increases the activity of the enzyme. Ketoconazole is a known inhibitor of Cytochrome P450 3A4 enzyme meaning that it decreases the activity of the enzyme.

In addition, the safety and tolerability of tasimelteon will also be assessed throughout the study.


Condition Intervention Phase
Healthy
Drug: tasimelteon
Drug: Rifampin
Drug: Ketoconazole
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: An Open-label, Single-sequence Study in Two Cohorts of Healthy Subjects to Evaluate the Single-dose Pharmacokinetics of Tasimelteon Alone and in Combination With a CYP3A4 Inhibitor, Ketoconazole, or a CYP3A4 Inducer, Rifampin.

Resource links provided by NLM:


Further study details as provided by Vanda Pharmaceuticals:

Primary Outcome Measures:
  • Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of tasimelteon and tasimelteon's metabolites with and without the CYP3A4 inhibitor ketoconazole. [ Time Frame: Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose. Days 6 and 7: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours post-dose ] [ Designated as safety issue: No ]
  • Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of tasimelteon and tasimelteon's metabolites with and without the CYP3A4 inducer rifampin. [ Time Frame: Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose. Days 12 and 13: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours post-dose ] [ Designated as safety issue: No ]

Enrollment: 48
Study Start Date: June 2012
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rifampin Drug: tasimelteon
20mg, oral capsule, once, Days 1 and 12
Other Name: VEC-162, BMS-214778
Drug: Rifampin
600mg, oral capsules (2 x 300mg), once daily (QD), Days 2-11
Experimental: Ketoconazole Drug: tasimelteon
20mg, oral capsule, once, Days 1 and 6
Other Name: VEC-162, BMS-214778
Drug: Ketoconazole
400mg, oral tablets (2 x 200mg), once daily (QD), Days 2-6

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Men and women ages 18 - 55 years, inclusive;
  2. Non-smokers;
  3. Subjects with Body Mass Index (BMI) of ≥18 and ≤35 kg/m^2;
  4. Males, non-fecund females, or females of child-bearing potential using an acceptable method of birth control for a period of 35 days before the first dosing;
  5. Vital signs which are within the ranges shown below:

    1. Body temperature between 35.0-37.5 °C;
    2. Systolic blood pressure between 90-150 mmHg;
    3. Diastolic blood pressure between 50-95 mmHg;
    4. Pulse rate between 50-100 bpm.
  6. Ability and acceptance to provide written informed consent;
  7. Willing and able to comply with study requirements and restrictions;
  8. In good health as determined by past medical history, physical examination, electrocardiogram, clinical laboratory tests and urinalysis;

Exclusion Criteria:

  1. History of recent (within six months) drug or alcohol abuse;
  2. Any major surgery within three months of Baseline or any minor surgery within one month;
  3. History or current evidence of cardiovascular, hepatic, hematopoietic, renal, gastrointestinal or metabolic dysfunction or psychiatric disease judged by the Investigator to be clinically significant;
  4. History (including family history) or current evidence of congenital long QT syndrome or known acquired QT interval prolongation;
  5. Subjects who are currently considered a suicide risk, any subject who has ever made a suicide attempt, or those who are currently demonstrating active (within the past 6 months) suicidal ideation;
  6. Any condition requiring the regular use of medication except those listed in Section 8.2 of the protocol;
  7. Exposure to any investigational drug, including placebo, within 30 days or 5 half-lives (whichever is longer) of baseline
  8. Exposure (within 2 weeks of the Baseline Visit) to any over-the-counter medications including melatonin, dietary supplements and/or herbal remedies, except those listed on Section 8.2;
  9. Treatment with any drug known to cause major organ system toxicity (e.g., chloramphenicol or tamoxifen) during the 60 days preceding the Screening visit;
  10. History of intolerance and/or hypersensitivity to ketaconazole, drugs similar to ketoconazole (e.g. miconzaole or fluconazole), rifampin, tasimelteon, and/or drugs similar to tasimelteon including melatonin;
  11. Donation or loss of 400 mL or more of blood within one month prior to the Baseline Visit;
  12. Significant illness within the two weeks prior to Baseline;
  13. Pregnant or lactating females;
  14. History of porphyria or liver disease and/or positive for one or more of the following serological results:

    1. A positive hepatitis C antibody test (anti-HCV)
    2. A positive hepatitis B surface antigen (HBsAg)
    3. A positive HIV test result
  15. Participation in a previous BMS-214778/VEC-162 trial;
  16. Use of any food or beverage containing grapefruit or grapefruit juice, apple or orange juice, vegetables from the mustard green family (e.g. kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard greens) and charbroiled meats for at least 2 weeks before the Baseline Visit until the end of the study;
  17. Inability to be venipunctured and/or tolerate venous access;
  18. Subjects who are unable to read or speak English;
  19. Any other sound medical reason as determined by the clinical Investigator.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01637636

Locations
United States, Missouri
QPS Bio-Kinetic Clinical Applications
Springfield, Missouri, United States, 65802
Sponsors and Collaborators
Vanda Pharmaceuticals
  More Information

No publications provided

Responsible Party: Vanda Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01637636     History of Changes
Other Study ID Numbers: VP-VEC-162-1112
Study First Received: June 28, 2012
Last Updated: February 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Vanda Pharmaceuticals:
rifampin,
ketoconazole,
CYP3A4,
tasimelteon,
VEC-162
Pharmacokinetics

Additional relevant MeSH terms:
Ketoconazole
Rifampin
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antitubercular
Anti-Bacterial Agents
Antitubercular Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014