Open Label Study to Assess the Absolute Bioavailability of Tasimelteon (HETLIOZ™)
Primary Purpose
Non-24-Hour-Sleep-Wake Disorder
Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
tasimelteon 20 mg capsule
tasimelteon 2 mg I.V.
Sponsored by
About this trial
This is an interventional basic science trial for Non-24-Hour-Sleep-Wake Disorder focused on measuring Non-24, absolute bioavailability, tasimelteon, Hetlioz™
Eligibility Criteria
Inclusion Criteria:
- Men and women ages 18 - 55 years, inclusive;
- Non-smokers [abstinence from smoking for at least 6 months before the screening visit] and test negative for cotinine at screening and baseline;
- Subjects with Body Mass Index (BMI) of ≥18 and ≤25 kg/m2 (BMI = weight (kg)/ [height (m)]2);
- 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
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 mmHg;
- Diastolic blood pressure between 50-95 mmHg;
- Pulse rate between 50-100 bpm.
- Ability and acceptance to provide written informed consent;
- Willing and able to comply with study requirements and restrictions;
- Subjects must be in good health as determined by past medical history, physical examination, electrocardiogram, clinical laboratory tests and urinalysis;
Exclusion Criteria:
- 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;
- Any major surgery within three months of the first Baseline visit or any minor surgery within one month;
- History or current evidence of cardiovascular, hepatic, hematopoietic, renal, gastrointestinal or metabolic dysfunction or psychiatric disease judged by the Investigator to be clinically significant;
- 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);
- Any condition requiring the regular use of medication except those listed in Section 8.2;
- Exposure to any investigational drug, including placebo, within 30 days or 5 half-lives (whichever is longer) of baseline
- 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;
- Treatment with any drug known to cause major organ system toxicity (e.g., chloramphenicol or tamoxifen) during the 60 days preceding the Screening visit;
- History of intolerance and/or hypersensitivity to tasimelteon, and/or drugs similar to tasimelteon including melatonin;
- Donation or loss of 400 mL or more of blood within one month prior to the Baseline Visit;
- Significant illness within the two weeks prior to Baseline;
- Pregnant or lactating females;
History of porphyria or liver disease and/or positive for one or more of the following serological results:
- A positive hepatitis C antibody test (anti-HCV)
- A positive hepatitis B surface antigen (HBsAg)
- A positive HIV test result
- 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;
- Inability to be venipunctured and/or tolerate venous access;
- Previous participation in a BMS-214778, VEC-162, or tasimelteon study;
- Subjects who are unable to read or speak English;
- Any other sound medical reason as determined by the clinical Investigator.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Sequence A
Sequence B
Arm Description
Single oral dose of tasimelteon 20 mg on Day 1 Single I.V. dose of tasimelteon 2 mg on Day 6
Single I.V. dose of tasimelteon 2 mg on Day 1 Single oral dose of tasimelteon 20 mg on Day 6
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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
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
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.
Number of Participants With Adverse Events
Number of participants with treatment-emergent adverse event per treatment arm and overall.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02130999
Brief Title
Open Label Study to Assess the Absolute Bioavailability of Tasimelteon (HETLIOZ™)
Official Title
A Single Dose, Open-Label, Randomized Two-Period Crossover Study in Healthy Young Subjects to Assess the Absolute Bioavailability of Tasimelteon (HETLIOZ™)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2016
Overall Recruitment Status
Completed
Study Start Date
May 2014 (undefined)
Primary Completion Date
May 2014 (Actual)
Study Completion Date
May 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vanda Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
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 what the body does to the drug. Blood samples will be taken throughout the study for PK analysis.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-24-Hour-Sleep-Wake Disorder
Keywords
Non-24, absolute bioavailability, tasimelteon, Hetlioz™
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sequence A
Arm Type
Experimental
Arm Description
Single oral dose of tasimelteon 20 mg on Day 1
Single I.V. dose of tasimelteon 2 mg on Day 6
Arm Title
Sequence B
Arm Type
Experimental
Arm Description
Single I.V. dose of tasimelteon 2 mg on Day 1
Single oral dose of tasimelteon 20 mg on Day 6
Intervention Type
Drug
Intervention Name(s)
tasimelteon 20 mg capsule
Other Intervention Name(s)
Hetlioz™ 20 mg
Intervention Type
Drug
Intervention Name(s)
tasimelteon 2 mg I.V.
Primary Outcome Measure Information:
Title
Absolute Bioavailability After a Single Oral Dose of Hetlioz™(Tasimelteon) 20mg
Description
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
Secondary Outcome Measure Information:
Title
Cmax of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration.
Description
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
Title
AUC (Inf) of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration.
Description
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
Title
T1/2 of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration.
Description
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
Title
Total Clearance of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration.
Description
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
Title
Cmax of Tasimelteon's Metabolites After an Oral and I.V. Dose of Tasimelteon
Description
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
Title
AUC(Inf) of Tasimelteon's Metabolites After a Single Oral and I.V. Dose
Description
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
Title
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
Description
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
Title
Number of Participants With Adverse Events
Description
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).
Other Pre-specified Outcome Measures:
Title
Number of Participants That Reported Suicidal Ideation, Suicidal Behavior, or Suicide Attempts.
Description
Number of Participants that reported suicidal ideation, suicidal behavior, or suicide attempts per treatment arm and overall.
Time Frame
Baseline to End of Study Day 5 (± 2 days).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Men and women ages 18 - 55 years, inclusive;
Non-smokers [abstinence from smoking for at least 6 months before the screening visit] and test negative for cotinine at screening and baseline;
Subjects with Body Mass Index (BMI) of ≥18 and ≤25 kg/m2 (BMI = weight (kg)/ [height (m)]2);
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
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 mmHg;
Diastolic blood pressure between 50-95 mmHg;
Pulse rate between 50-100 bpm.
Ability and acceptance to provide written informed consent;
Willing and able to comply with study requirements and restrictions;
Subjects must be in good health as determined by past medical history, physical examination, electrocardiogram, clinical laboratory tests and urinalysis;
Exclusion Criteria:
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;
Any major surgery within three months of the first Baseline visit or any minor surgery within one month;
History or current evidence of cardiovascular, hepatic, hematopoietic, renal, gastrointestinal or metabolic dysfunction or psychiatric disease judged by the Investigator to be clinically significant;
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);
Any condition requiring the regular use of medication except those listed in Section 8.2;
Exposure to any investigational drug, including placebo, within 30 days or 5 half-lives (whichever is longer) of baseline
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;
Treatment with any drug known to cause major organ system toxicity (e.g., chloramphenicol or tamoxifen) during the 60 days preceding the Screening visit;
History of intolerance and/or hypersensitivity to tasimelteon, and/or drugs similar to tasimelteon including melatonin;
Donation or loss of 400 mL or more of blood within one month prior to the Baseline Visit;
Significant illness within the two weeks prior to Baseline;
Pregnant or lactating females;
History of porphyria or liver disease and/or positive for one or more of the following serological results:
A positive hepatitis C antibody test (anti-HCV)
A positive hepatitis B surface antigen (HBsAg)
A positive HIV test result
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;
Inability to be venipunctured and/or tolerate venous access;
Previous participation in a BMS-214778, VEC-162, or tasimelteon study;
Subjects who are unable to read or speak English;
Any other sound medical reason as determined by the clinical Investigator.
12. IPD Sharing Statement
Learn more about this trial
Open Label Study to Assess the Absolute Bioavailability of Tasimelteon (HETLIOZ™)
We'll reach out to this number within 24 hrs