Pharmacokinetics of Tasimelteon Alone and in Combination With CYP1A2 Inhibitor, Fluvoxamine

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Vanda Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01540500
First received: February 22, 2012
Last updated: February 14, 2014
Last verified: February 2014
  Purpose

The purpose of this research study is to evaluate whether administration of a CYP1A2 inhibitor affects the single-dose pharmacokinetics of tasimelteon and its metabolites. The safety and tolerability of tasimelteon will also be assessed throughout the study.


Condition Intervention Phase
Healthy Volunteers
Drug: Tasimelteon
Drug: Fluvoxamine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: An Open-label, Single-sequence Study in Healthy Subjects to Evaluate the Single-dose Pharmacokinetics of Tasimelteon Alone and in Combination With a CYP1A2 Inhibitor, Fluvoxamine

Resource links provided by NLM:


Further study details as provided by Vanda Pharmaceuticals:

Primary Outcome Measures:
  • Tasimelteon pharmacokinetic parameters (AUC, Cmax, Tmax) [ Time Frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 7, 8, 10, 12 and 24 hours post-dose. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and tolerability as measured by spontaneous reporting of AEs, and clinically significant changes in laboratory parameters, ECG parameters, and vital signs [ Time Frame: Days 1-9 ] [ Designated as safety issue: Yes ]
  • The Columbia Suicide Severity Rating Scale will be used to assess suicidal behavior and ideation. [ Time Frame: Screening, Day -1 (baseline), and Day 9 (end of study) ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic parameters (AUC, Cmax, Tmax) of tasimelteon metabolites M9, M11, M12, M13, and M14 [ Time Frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 7, 8, 10, 12 and 24 hours post-dose. ] [ Designated as safety issue: No ]
  • Fluvoxamine pharmacokinetic parameters (AUC, Cmax, Tmax) [ Time Frame: Pre-dose, 1, 3, 4, 6, 8, 12, and 24 hours post-dose ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: February 2012
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Steady State PK Group Drug: Tasimelteon
5.66 mg dose on Day 1 and Day 8
Other Names:
  • VEC-162
  • BMS-214778
Drug: Fluvoxamine
50 mg Dose on Days 2-8

  Eligibility

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

Inclusion Criteria:

  1. Men or women between 18 - 55 years, inclusive;
  2. Non-smokers [abstinence from smoking for at least 6 months before the screening visit] and test negative for cotinine at screening and baseline;
  3. Subjects with Body Mass Index (BMI) of ≥18 and ≤35 kg/m2 (BMI = weight (kg)/ [height (m)]2);
  4. Males, non-fecund females (i.e., surgically sterilized, if procedure was done 6 months before screening or subject is postmenopausal, without menses for 6 months before screening), or females of child-bearing potential using an acceptable method of birth control for a period of 35 days before the first dosing and females must have a negative pregnancy test at the screening and baseline visits;
  5. Note 1: Acceptable methods of birth control include any one of the following: abstinence, vasectomized sexual partner, hormonal methods (i.e. pill, hormonal IUD, Depo-Provera, implants, patch, intravaginal device [NuvaRing]), intrauterine device (IUD [copper banded coils]), diaphragm, cervical cap, or condom with spermicidal jelly or foam.
  6. Vital signs (after 3 minutes resting in a semi-supine position) which are within the ranges shown below:

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

Exclusion Criteria:

  1. History of recent (within six months) drug or alcohol abuse as defined in DSM IV, Diagnostic Criteria for Drug and Alcohol Abuse or evidence of such abuse as indicated by the laboratory assays conducted during the Screening Visit or at Baseline;
  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 judged by the Investigator to be clinically significant;
  4. 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 last year) suicidal ideation as deemed by the Columbia Suicide Severity Rating Scale (C-SSRS);
  5. Any condition requiring the regular use of medication except those listed on Section 8.2;
  6. Exposure to any investigational drug, including placebo, within 30 days or 5 half-lives (whichever is longer) of baseline;
  7. Anyone who has taken a melatonin preparation chronically within the past two months prior to Day 1;
  8. Donation or loss of 400 mL or more of blood within two months prior to the Baseline Visit;
  9. Significant illness within the two weeks prior to Baseline;
  10. A known intolerance or hypersensitivity to fluvoxamine, tasimelteon or drugs similar to tasimelteon (including melatonin) or fluvoxamine;
  11. Pregnant or lactating females;
  12. History of liver disease and/or positive for one or more of the following serological results:

    • A positive hepatitis C antibody test (anti-HCV)
    • A positive hepatitis B surface antigen (HBsAg)
    • A positive HIV test result
  13. Exposure (within 2 weeks of the Baseline Visit) of any over-the-counter medications including dietary supplements and/or herbal remedies, except those listed on Section 8.2;
  14. Treatment with any drug known to cause major organ system toxicity (e.g., chloramphenicol or tamoxifen) during the 60 days preceding the Screening visit;
  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
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01540500

Locations
United States, Missouri
Bio-Kinetic Clinical Applications
Springfield, Missouri, United States, 65802
Sponsors and Collaborators
Vanda Pharmaceuticals
Investigators
Study Director: Vanda Pharmaceuticals Vanda Pharmaceuticals
  More Information

No publications provided

Responsible Party: Vanda Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01540500     History of Changes
Other Study ID Numbers: VP-VEC-162-1111
Study First Received: February 22, 2012
Last Updated: February 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Vanda Pharmaceuticals:
Pharmacokinetics
Drug Interaction

Additional relevant MeSH terms:
Fluvoxamine
Anti-Anxiety Agents
Antidepressive Agents
Antidepressive Agents, Second-Generation
Central Nervous System Agents
Central Nervous System Depressants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Uptake Inhibitors
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on October 29, 2014