Clinical Trial: Open Label Study to Assess the Absolute Bioavailability of Tasimelteon (HETLIOZ™)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Single Dose, Open-Label, Randomized Two-Period Crossover Study in Healthy Young Subjects to Assess the Absolute Bioavailability of Tasimelteon (HETLIOZ™)

Brief Summary:

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

Detailed Summary:
Sponsor: Vanda Pharmaceuticals

Current Primary Outcome: Absolute Bioavailability After a Single Oral Dose of Hetlioz™(Tasimelteon) 20mg [ 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 ]

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.


Original Primary Outcome: To assess the absolute bioavailability after a single oral dose of Hetlioz™(tasimelteon) 20mg [ Time Frame: From baseline to Day 5 (±2) ]

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.


Current Secondary Outcome:

  • Cmax of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration. [ 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 will be compared when given orally or administered as an I.V.
  • AUC (Inf) of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration. [ 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 will be compared when given orally or administered as an I.V.
  • T1/2 of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration. [ 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 ]
    T1/2 of tasimelteon will be compared when given orally or administered as an I.V.
  • Total Clearance of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration. [ 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 ]
    CL of tasimelteon will be compared when given orally or administered as an I.V.
  • Cmax of Tasimelteon's Metabolites After an Oral and I.V. Dose 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 ]
    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
  • AUC(Inf) of Tasimelteon's Metabolites After a Single Oral and I.V. Dose [ 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 ]
    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
  • 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 [ 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 ]
    Comparison of the metabolite-to-parent AUC(inf) ratios for the oral and IV routes.
  • Number of Participants With Adverse Events [ Time Frame: From Baseline to End of Study; Day 5 (± 2 days). ]
    Number of participants with treatment-emergent adverse event per treatment arm and overall.


Original Secondary Outcome:

  • To evaluate the single-dose pharmacokinetics of tasimelteon after a single 20 mg oral dose and after a single 2 mg I.V. administration. [ Time Frame: From baseline to Day 5 (± 2 days). ]
    Plasma concentrations and pharmacokinetic parameters of tasimelteon will be compared when given orally or administered as an I.V.
  • 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. [ Time Frame: From baseline to Day 5 (± 2 days). ]
    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.
  • To evaluate the safety and tolerability of a single oral dose of tasimelteon 20 mg. [ Time Frame: From Baseline to End of Study; Day 5 (± 2 days). ]
    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.
  • To evaluate the safety and tolerability of an I.V. administration of tasimelteon 2 mg. [ Time Frame: From baseline to End of Study; Day 5 (± 2 days). ]
    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.


Information By: Vanda Pharmaceuticals

Dates:
Date Received: May 1, 2014
Date Started: May 2014
Date Completion:
Last Updated: July 21, 2016
Last Verified: July 2016