Evaluation of the Pharmacodynamic and Pharmacokinetic Interactions of Tasimelteon and Ethanol

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Vanda Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01578057
First received: April 12, 2012
Last updated: February 14, 2014
Last verified: February 2014
  Purpose

The purpose of this research study is to understand if there is any difference in the effects of tasimelteon when it is taken alone or in combination with alcohol. This research study is also being done to understand if there is any difference in the amount of tasimelteon (and its breakdown products) or alcohol in the blood when taken alone or together. Finally, the study will also look at the safety and tolerability (how acceptable it is) of tasimelteon.


Condition Intervention Phase
Pharmacodyamics and Pharmacokinetics of Tasimelteon Alone and in Combination With Ethanol
Drug: tasimelteon
Drug: Ethanol
Other: Placebo tasimelteon
Drug: Placebo ethanol
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: A Randomized, Double-mask, Four-period Crossover Study in Healthy Subjects to Evaluate the Pharmacodynamic and Pharmacokinetic Interactions of Tasimelteon and Ethanol

Resource links provided by NLM:


Further study details as provided by Vanda Pharmaceuticals:

Primary Outcome Measures:
  • Pharmacodynamic parameters (Digit Vigilance, Digit Symbol Substitution Task, Hopkins Verbal Learning Test Revised , Divided Attention Test, Balance Platform Test, Choice Reaction Time, Visual Analog Scale) as measured by peak change from baseline [ Time Frame: Days 1, 8, 15, 22: at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8, 12, and 24 hours after dose ] [ Designated as safety issue: Yes ]

    Differences will be calculated for the following comparisons:

    • Ethanol Alone vs. Placebo-Placebo
    • Ethanol Alone vs. Tasimelteon + Ethanol
    • Tasimelteon Alone vs. Placebo-Placebo
    • Tasimelteon Alone vs. Tasimelteon + Ethanol


Secondary Outcome Measures:
  • Pharmacokinetic parameters (AUC, Cmax, Tmax) of tasimelteon, tasimelteon's metabolites, and ethanol [ Time Frame: Approximately Days 1, 8, 15, and 22: predose, 0.25, 0.75, 1, 1.5, 2, 3, 4, 8, 12, and 24 hours after dosing ] [ Designated as safety issue: No ]
  • Safety and tolerability as measured by spontaneous reporting of AEs, and clinically significant changes in laboratory parameters, ECG parameters, and vital signs [ Time Frame: Screening (approximately Day -10), Days -2, -1, 1, and approximately Days 8, 15, 22, 23 ] [ Designated as safety issue: Yes ]
  • The Columbia-Suicide Severity Rating Scale will be used to assess suicidal behavior and ideation. [ Time Frame: once per day at Screening (approximately day -7),Day -1 (baseline), approximately Days 1, 8, 15, 22 and 23 (end of study) ] [ Designated as safety issue: Yes ]

Enrollment: 28
Study Start Date: April 2012
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: tasimelteon + placebo ethanol Drug: tasimelteon
20mg, once
Other Names:
  • VEC-162
  • BMS-214778
Drug: Placebo ethanol
A total volume of 300 mL as a light cranberry cocktail (consumed within 15 minutes) with about 1 mL of supernatant of ethanol in the top
Experimental: ethanol + placebo tasimelteon Drug: Ethanol
0.6 g/kg ethanol (women) or 0.7 g/kg ethanol (men) in a total volume of 300 mL as a light cranberry juice cocktail, (consumed within 15 minutes).
Other Name: vodka
Other: Placebo tasimelteon
once
Experimental: tasimelteon + ethanol Drug: tasimelteon
20mg, once
Other Names:
  • VEC-162
  • BMS-214778
Drug: Ethanol
0.6 g/kg ethanol (women) or 0.7 g/kg ethanol (men) in a total volume of 300 mL as a light cranberry juice cocktail, (consumed within 15 minutes).
Other Name: vodka
Experimental: placebo tasimelteon + placebo ethanol Other: Placebo tasimelteon
once
Drug: Placebo ethanol
A total volume of 300 mL as a light cranberry cocktail (consumed within 15 minutes) with about 1 mL of supernatant of ethanol in the top

Detailed Description:

Alcohol is a drug that gets absorbed into the bloodstream quickly. The blood carries the alcohol to the brain where it slows down the messages in the brain (alcohol is a depressant). Alcohol affects a person's memory, behaviour, concentration, alertness (your thought process is slower), and coordination (your movements become clumsy). The intended effect of tasimelteon is to cause sleepiness. Sleepiness may result in similar effects on memory, concentration, alertness, and coordination as alcohol. There is the possibility taking tasimelteon and alcohol together can make these effects stronger or worse.

  Eligibility

Ages Eligible for Study:   19 Years to 79 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Ability and acceptance to provide written informed consent;
  2. Men or women between 19- 75 years, inclusive;
  3. Subjects with Body Mass Index (BMI) of ≥18.0 and ≤35.0 kg/m2 (BMI = weight (kg)/ [height (m)]2) and weigh a minimum of 50 kg (110 pounds);
  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; Note: 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.
  5. Social or moderate drinkers who drink on average 7 to 21 units of alcohol per week and have consumed more than 4 (women) or 5 (men) units of alcohol on at least one occasion in the last month; Note: One unit of alcohol is equivalent to 1.5 oz of hard liquor or 5 oz of wine or 12 oz of beer.
  6. Willing and able to comply with study requirements and restrictions;
  7. Subjects must be in good health as determined by past medical history, physical examination, electrocardiogram, clinical laboratory tests and urinalysis;
  8. Vital signs (after 3 minutes resting in a semi-supine or seated position) which are within the ranges shown below:

    1. Body temperature between 35.0-37.5 °C;
    2. Systolic blood pressure between 90-150 mm Hg;
    3. Diastolic blood pressure between 50-95 mm Hg;
    4. Pulse rate between 40-100 bpm.

Exclusion Criteria:

  1. Subjects who are not able to tolerate [0.6 g/kg for female/0.7 g/kg for men] ethanol during the Qualification visit. Intolerance is defined as ≥ 1 vomiting episode or severe nausea.
  2. Current (within 12 months) drug or alcohol abuse or dependence 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;
  3. Any major surgery within three months of Baseline or any minor surgery within one month;
  4. History or current evidence of pulmonary, cardiovascular, hepatic, hematopoietic, renal, gastrointestinal or metabolic dysfunction judged by the Investigator to be clinically significant;
  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 last year) suicidal ideation as deemed by the Columbia Suicide Severity Rating Scale (C-SSRS);
  6. Any condition requiring the regular use of medication;
  7. Subjects who have used tobacco products 3 months prior to Baseline. Smokers will be defined as any subject who reports cigarette, tobacco, nicotine gum, or nicotine patch use;
  8. Exposure to any investigational drug, including placebo, within 30 days or 5 half-lives (whichever is longer) of Baseline;
  9. Donation or loss of 400 mL or more of blood within two months prior to the Baseline Visit;
  10. Significant illness within the two weeks prior to Baseline;
  11. A known intolerance or hypersensitivity to tasimelteon or drugs similar to tasimelteon including melatonin;
  12. Pregnant or lactating females;
  13. History of liver disease and/or positive for one or more of the following serological results:

    1. A positive hepatitis B surface antigen (HBsAg)
    2. A positive hepatitis C antibody test (anti-HCV)
    3. A positive HIV test result;
  14. Use of prescription or OTC medication, including melatonin and herbal products (e.g., St. John's Wort) within 2 weeks of the Baseline Visit;
  15. Treatment with any drug known to cause major organ system toxicity (e.g., chloramphenicol or tamoxifen) during the 60 day preceding the Screening visit;
  16. Participation in a previous BMS-214778/VEC-162 trial;
  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: NCT01578057

Locations
Canada, Ontario
INC Research Toronto, Inc.
Toronto, Ontario, Canada, M5V 2TC
Sponsors and Collaborators
Vanda Pharmaceuticals
  More Information

No publications provided

Responsible Party: Vanda Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01578057     History of Changes
Other Study ID Numbers: VP-VEC-162-1108
Study First Received: April 12, 2012
Last Updated: February 14, 2014
Health Authority: Canada: Health Canada
United States: Food and Drug Administration

Keywords provided by Vanda Pharmaceuticals:
alcohol

Additional relevant MeSH terms:
Ethanol
Anti-Infective Agents, Local
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Central Nervous System Depressants
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 18, 2014