Non-24-Hour-Sleep-Wake Disorder Clinical Trial
Official title:
A Single Dose, Open-Label, Randomized Two-Period Crossover Study in Healthy Young Subjects to Assess the Absolute Bioavailability of Tasimelteon (HETLIOZ™)
| Verified date | May 2014 |
| Source | Vanda Pharmaceuticals |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | United States: Food and Drug Administration |
| Study type | Interventional |
Hetlioz™ (tasimelteon) is used in the treatment of Non-24-Hour-Sleep-Wake Disorder (Non-24).
Non-24 is very common in people who are totally blind because light can not reset their body
clock. This causes the internal sleep-wake cycle to be out of sync with the 24-hour
day-night. Non-24 is a serious, chronic circadian rhythm disorder in the blind that causes
nighttime sleep problems and a wide range of daytime difficulties, including an overwhelming
urge to nap.
Tasimelteon will be given in two ways; orally (by mouth) as a 20 mg capsule and
intravenously (I.V.) by infusion through a catheter (not an injection) into a vein. The oral
administration is approved by the FDA. The I.V. administration is considered investigational
as it has not been approved by the FDA. This will be the first time tasimelteon will be
given to humans by intravenous (I.V.) injection.
The purposes of this research study are to:
- assess how quickly a single 20 mg oral dose of tasimelteon is absorbed into the body;
- evaluate the single-dose pharmacokinetics of tasimelteon after a single 20 mg oral dose
and after a single 2 mg I.V. dose;
- evaluate the single-dose pharmacokinetics of tasimelteon metabolites after a single 20
mg oral dose and after a single 2 mg I.V. dose;
- evaluate the safety and tolerability of a single 20 mg oral dose of tasimelteon; and
- evaluate the safety and tolerability of a single 2 mg I.V. dose of tasimelteon.
Pharmacokinetics (PK) is the study of how a drug is absorbed, distributed, metabolized, and
eventually eliminated by the body. Pharmacokinetics is what the body does to the drug. Blood
samples will be taken throughout the study for PK analysis.
| Status | Completed |
| Enrollment | 14 |
| Est. completion date | May 2014 |
| Est. primary completion date | May 2014 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | Both |
| Age group | 18 Years to 55 Years |
| Eligibility |
Inclusion Criteria: 1. Men and women ages 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 =25 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; 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 5. Vital signs (after 3 minutes resting in a semi-supine position) 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. Subjects must be 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 as defined in DSM-V, 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 the first Baseline visit 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. 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 as deemed by the Columbia Suicide Severity Rating Scale (C-SSRS); 5. Any condition requiring the regular use of medication except those listed in Section 8.2; 6. Exposure to any investigational drug, including placebo, within 30 days or 5 half-lives (whichever is longer) of baseline 7. Exposure (within 2 weeks of Day -1) to any over-the-counter medications including melatonin, dietary supplements and/or herbal remedies, except those listed on Section 8.2; 8. Treatment with any drug known to cause major organ system toxicity (e.g., chloramphenicol or tamoxifen) during the 60 days preceding the Screening visit; 9. History of intolerance and/or hypersensitivity to tasimelteon, and/or drugs similar to tasimelteon including melatonin; 10. Donation or loss of 400 mL or more of blood within one month prior to the Baseline Visit; 11. Significant illness within the two weeks prior to Baseline; 12. Pregnant or lactating females; 13. 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 14. 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; 15. Inability to be venipunctured and/or tolerate venous access; 16. Previous participation in a BMS-214778, VEC-162, or tasimelteon study; 17. Subjects who are unable to read or speak English; 18. Any other sound medical reason as determined by the clinical Investigator. |
Allocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science
| Country | Name | City | State |
|---|---|---|---|
| n/a | |||
| Lead Sponsor | Collaborator |
|---|---|
| Vanda Pharmaceuticals |
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | The Columbia-Suicide Severity Scale (C-SSRS) will be used to assess suicidal behavior and ideation. | Baseline to End of Study Day 5 (± 2 days). | Yes | |
| Primary | To assess the absolute bioavailability after a single oral dose of Hetlioz™(tasimelteon) 20mg | The absolute bioavailability (F) of tasimelteon will be estimated from the dose-corrected AUC(inf) after oral and I.V. administration using an analysis of variance (ANOVA) model with treatment, period, sequence, and subject within sequence as the classification variables, using natural log-transformed data. The geometric mean ratio (GMR), oral-to-I.V., and its associated 90% confidence interval (CI) will be used as the estimate of F and its variability. | From baseline to Day 5 (±2) | No |
| Secondary | To evaluate the single-dose pharmacokinetics of tasimelteon after a single 20 mg oral dose and after a single 2 mg I.V. administration. | Plasma concentrations and pharmacokinetic parameters of tasimelteon will be compared when given orally or administered as an I.V. | From baseline to Day 5 (± 2 days). | No |
| Secondary | To evaluate the single-dose pharmacokinetics of tasimelteon metabolites M9, M11, M12, M13, and M14 after a single 20 mg oral dose and after a 2 mg I.V. administration of tasimelteon. | Plasma concentrations and pharmacokinetic parameters of tasimelteon metabolites M9, M11, M12, M13 and M14 will be compared when given orally or administered as an I.V. | From baseline to Day 5 (± 2 days). | No |
| Secondary | To evaluate the safety and tolerability of a single oral dose of tasimelteon 20 mg. | Safety and tolerability of a single 20 mg oral dose of tasimelteon will be assessed as follows: subjective tolerability from spontaneous reporting of Adverse Events, changes in clinical laboratory parameters that are relevant to safety and influence of trial medication on vital signs and ECG parameters. | From Baseline to End of Study; Day 5 (± 2 days). | Yes |
| Secondary | To evaluate the safety and tolerability of an I.V. administration of tasimelteon 2 mg. | Safety and tolerability of 2 mg tasimelteon administered as an I.V. will be assessed as follows: subjective tolerability from spontaneous reporting of AEs, changes in clinical laboratory parameters that are relevant to safety and influence of trial medication on vital signs and ECG parameters. | From baseline to End of Study; Day 5 (± 2 days). | Yes |