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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
14
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.
Time frame: pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose
Cmax of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration.
Cmax of tasimelteon will be compared when given orally or administered as an I.V.
Time frame: pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose
AUC (Inf) of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration.
AUC (inf) of Tasimelteon will be compared when given orally or administered as an I.V.
Time frame: pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose
T1/2 of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration.
T1/2 of tasimelteon will be compared when given orally or administered as an I.V.
Time frame: pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours pos-dose
Total Clearance of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration.
CL of tasimelteon will be compared when given orally or administered as an I.V.
Time frame: pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose
Cmax of Tasimelteon's Metabolites After an Oral and I.V. Dose of Tasimelteon
The mean +/- SD for the Cmax of tasimelteon's metabolites after a single 20 mg oral dose of tasimelteon and after a single 2 mg I.V. administration of tasimelteon
Time frame: pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose
AUC(Inf) of Tasimelteon's Metabolites After a Single Oral and I.V. Dose
The mean +/- SD for the AUC(inf) of tasimelteon's metabolites after a single 20 mg oral dose of tasimelteon and after a single 2 mg I.V. administration of tasimelteon
Time frame: pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose
Metabolite-to-parent AUC(Inf) Ratios After Oral Administration of a Single 20 mg Dose and IV Administration of a Single 2 mg Dose of Tasimelteon
Comparison of the metabolite-to-parent AUC(inf) ratios for the oral and IV routes.
Time frame: pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose
Number of Participants With Adverse Events
Number of participants with treatment-emergent adverse event per treatment arm and overall.
Time frame: From Baseline to End of Study; Day 5 (± 2 days).
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.