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

NCT01540500 | Completed Phase 1

• 1 other identifier: VP-VEC-162-1111
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Volunteers

Keywords

Pharmacokinetics; Drug Interaction

Outcome Measures

Primary Outcomes (1)

• Tasimelteon pharmacokinetic parameters (AUC, Cmax, Tmax)

  Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 7, 8, 10, 12 and 24 hours post-dose.

Secondary Outcomes (4)

• Safety and tolerability as measured by spontaneous reporting of AEs, and clinically significant changes in laboratory parameters, ECG parameters, and vital signs

  Days 1-9

• The Columbia Suicide Severity Rating Scale will be used to assess suicidal behavior and ideation.

  Screening, Day -1 (baseline), and Day 9 (end of study)

• Pharmacokinetic parameters (AUC, Cmax, Tmax) of tasimelteon metabolites M9, M11, M12, M13, and M14

  Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 7, 8, 10, 12 and 24 hours post-dose.

• Fluvoxamine pharmacokinetic parameters (AUC, Cmax, Tmax)

  Pre-dose, 1, 3, 4, 6, 8, 12, and 24 hours post-dose

Study Arms (1)

Steady State PK Group

EXPERIMENTAL

Drug: Tasimelteon; Drug: Fluvoxamine

Interventions

Tasimelteon DRUG

5.66 mg dose on Day 1 and Day 8

Also known as: VEC-162, BMS-214778

Steady State PK Group

Fluvoxamine DRUG

50 mg Dose on Days 2-8

Steady State PK Group

Eligibility Criteria

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

You may qualify if:

• Men or women between 18 - 55 years, inclusive;
• Non-smokers \[abstinence from smoking for at least 6 months before the screening visit\] and test negative for cotinine at screening and baseline;
• Subjects with Body Mass Index (BMI) of ≥18 and ≤35 kg/m2 (BMI = weight (kg)/ \[height (m)\]2);
• 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;
• 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.
• 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.
• Ability and acceptance to provide written informed consent;
• Willing and able to comply with study requirements and restrictions;
• Subjects must be in good health as determined by past medical history, physical examination, electrocardiogram, clinical laboratory tests.

You may not qualify if:

• 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;
• Any major surgery within three months of Baseline or any minor surgery within one month;
• History or current evidence of cardiovascular, hepatic, hematopoietic, renal, gastrointestinal or metabolic dysfunction judged by the Investigator to be clinically significant;
• 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);
• Any condition requiring the regular use of medication except those listed on Section 8.2;
• Exposure to any investigational drug, including placebo, within 30 days or 5 half-lives (whichever is longer) of baseline;
• Anyone who has taken a melatonin preparation chronically within the past two months prior to Day 1;
• Donation or loss of 400 mL or more of blood within two months prior to the Baseline Visit;
• Significant illness within the two weeks prior to Baseline;
• A known intolerance or hypersensitivity to fluvoxamine, tasimelteon or drugs similar to tasimelteon (including melatonin) or fluvoxamine;
• Pregnant or lactating females;
• 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

Sponsors & Collaborators

• Vanda Pharmaceuticals: lead

Study Sites (1)

Bio-Kinetic Clinical Applications

Springfield, Missouri, 65802, United States

Location

MeSH Terms

Interventions

tasimelteon; Fluvoxamine

Intervention Hierarchy (Ancestors)

Oximes; Hydroxylamines; Amines; Organic Chemicals

Study Officials

• Vanda Pharmaceuticals

  Vanda Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2012
• First Posted: February 28, 2012
• Study Start: February 1, 2012
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: February 17, 2014

Record last verified: 2014-02

Locations

US (1)