A Study to Assess the Effect Tasimelteon on the Cytochrome P450 3A4 and 2C8 Enzymes in Healthy Subjects

NCT01402076 | Completed Phase 1

• 1 other identifier: VP-VEC-162-1110
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to understand whether there is any difference in the amount of midazolam (including its breakdown product) in the blood when midazolam is given with tasimelteon, and whether there is any difference in the amount of rosiglitazone in the blood when rosiglitazone is given with tasimelteon.

Conditions

Healthy Volunteers

Keywords

Pharmacokinetics; Drug Interaction

Outcome Measures

Primary Outcomes (2)

• CYP3A4 Pharmacokinetics

  Composite of 24 hour pharmacokinetic parameters of midazolam will be compared between Day 1 and Day 18.

  Days 1 and 18

• CYP2C8 Pharmacokinetics

  Composite of 24 hour pharmacokinetic parameters of rosiglitazone will be compared between Day 3 and 20.

  Days 3 and 20

Secondary Outcomes (4)

• Midazolam PK

  Days 1 and 17

• Rosiglitazone PK

  Days 3 and 20

• Tasimelteon multiple dose pharmacokinetics

  Days 4-21

• Tasimelteon safety and tolerability

  Days 1-21

Study Arms (2)

Steady State PK Group

EXPERIMENTAL

Drug: Tasimelteon; Drug: Rosiglitazone; Drug: Midazolam

No steady state PK

EXPERIMENTAL

Drug: Tasimelteon; Drug: Rosiglitazone; Drug: Midazolam

Interventions

Tasimelteon DRUG

20mg daily dosing, Days 4-20

No steady state PK; Steady State PK Group

Rosiglitazone DRUG

4mg, single dose, Days 3 and 20

Also known as: Avandia

No steady state PK; Steady State PK Group

Midazolam DRUG

10mg, single dose, Days 1 and 18

No steady state PK; 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:

• Ability and acceptance to provide written informed consent;
• Subjects must be males or females between 18 and 55 years of age, inclusive;
• Female subjects of childbearing potential must be non-pregnant and non-lactating and have a negative serum or urine pregnancy test at the Screening visit and at Check-in (Days -1) and agree not to attempt to become pregnant during the course of the study. Female subjects of childbearing potential (including peri-menopausal women who have had a menstrual bleeding within 1 year) must be using appropriate birth control (e.g. intrauterine device \[IUD\], diaphragm or condom with spermicidal jelly or foam or abstinence, or cervical cap) for a period of 35 days before the first dosing, for the duration of the study, and for one month after the last dose;
• a. Note: Women are not permitted to use hormonal methods of birth control (e.g. oral contraceptives, hormonal intrauterine device \[IUD\], patch and steroids) and must use another acceptable method of birth control during the study and for one month after the last dose. Women currently taking oral contraceptives will be required to discontinue their regimen two weeks prior to first dosing.
• Subjects with Body Mass Index (BMI) of \>18 and \<35 kg/m2 (BMI = weight (kg)/ \[height (m)\]2);
• 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 mm Hg;
• Diastolic blood pressure between 50-95 mm Hg;
• Pulse rate between 50-100 bpm.
• Willing and able to comply with study requirements;
• Subjects must be in good health as determined by past medical history, physical examination, electrocardiogram, clinical laboratory tests and urinalysis;

You may not qualify if:

• History of recent (within six months) drug or alcohol abuse;
• Any major surgery within three months of Day 1 or any minor surgery within one month;
• Donation or loss of 400 mL or more of blood within two months prior to the Baseline Visit;
• History or current evidence of cardiovascular, hepatic, hematopoietic, renal, gastrointestinal or metabolic dysfunction judged by the Investigator to be clinically significant;
• Any condition requiring the regular use of medication;
• History of intolerance and/or hypersensitivity to drugs including midazolam, rosiglitazone or other 'glitazones', melatonin or melatonin agonists, or anyone who has taken a melatonin preparation chronically within the past two months prior to Day 1;
• History of or current evidence of hypoglycemia judged by the Investigator to be clinically significant;
• History of liver disease and/or positive for one or more of the following serological results: HCV, HIV, HBsAg
• Treatment with any drug known to cause major organ system toxicity (e.g., chloramphenicol or tamoxifen) during the 60 day preceding Day 1;
• Elevated (\> 2 times the upper limit of normal) liver function tests (i.e. aspartate aminotransferase (AST \[SGOT\]), alanine aminotransferase (ALT \[SGPT\]), and total bilirubin);
• Inability to be venipunctured and/or tolerate venous access;
• Subjects who have used tobacco products 3 months prior to dosing.
• Exposure to any investigational drug within 30 days or 5 half lives (whichever is longer) of baseline, including placebo;
• Participation in a previous BMS-214778/VEC-162 trial;
• Use of prescription or OTC medication, including herbal products (e.g., St. John's Wort) within 2 weeks of Day 1;

Sponsors & Collaborators

• Vanda Pharmaceuticals: lead

Study Sites (1)

Bio-Kinetic Clinical Applications

Springfield, Missouri, 65802, United States

Location

MeSH Terms

Interventions

tasimelteon; Rosiglitazone; Midazolam

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Vanda Pharmaceuticals

  Vanda Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2011
• First Posted: July 26, 2011
• Study Start: August 1, 2011
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: February 17, 2014

Record last verified: 2014-02

Locations

US (1)