Non-24-Hour-Sleep-Wake DisorderPhase 4NCT02130999

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

A Phase 4 study testing tasimelteon 20 mg capsule and tasimelteon 2 mg I.V. in people with Non-24-Hour-Sleep-Wake Disorder, run by Vanda Pharmaceuticals.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Non-24-Hour-Sleep-Wake Disorder
What is being tested?: tasimelteon 20 mg capsule and tasimelteon 2 mg I.V.
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 14 participants
Where: No sites listed yet
Study dates: May 2014to May 2014
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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;

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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;

Who cannot join

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

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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.

About this study

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

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.

Conditions: Non-24-Hour-Sleep-Wake Disorder
Being tested: tasimelteon 20 mg capsule, tasimelteon 2 mg I.V.
Keywords: Non-24, absolute bioavailability, tasimelteon, Hetlioz™
Medical subject headings: Sleep Disorders, Circadian Rhythm

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

tasimelteon 20 mg capsuleDrug
Also called Hetlioz™ 20 mg
tasimelteon 2 mg I.V.Drug

Study groups in NCT02130999
Study group	Role	What they receive
Sequence A	Experimental	* Single oral dose of tasimelteon 20 mg on Day 1 * Single I.V. dose of tasimelteon 2 mg on Day 6 Receives: Drug: tasimelteon 20 mg capsule; Drug: tasimelteon 2 mg I.V.
Sequence B	Experimental	* Single I.V. dose of tasimelteon 2 mg on Day 1 * Single oral dose of tasimelteon 20 mg on Day 6 Receives: Drug: tasimelteon 20 mg capsule; Drug: tasimelteon 2 mg I.V.

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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 outcomes (8)

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: From Baseline to End of Study; Day 5 (± 2 days).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2014May 2014

First posted6 May 2014 (estimated)
Study startMay 2014
Primary completionMay 2014
Study completionMay 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Non-24-Hour-Sleep-Wake DisorderStudies of the same condition, open and under way.
More trials run by Vanda PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 14 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02130999
Sponsor's protocol ID: VP-VEC-162-4101
Status last verified: Jul 2016
First submitted: 1 May 2014
Last updated: 22 Aug 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Study at a glance

From the registry record, last updated by the sponsor on 22 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Single Dose, Open-Label, Randomized Two-Period Crossover Study in Healthy Young Subjects to Assess the Absolute Bioavailability of Tasimelteon (HETLIOZ™)
ClinicalTrials.gov ID: NCT02130999
Acronym / sponsor ID: VP-VEC-162-4101
Conditions: Non-24-Hour-Sleep-Wake Disorder
Keywords: Non-24, absolute bioavailability, tasimelteon, Hetlioz™
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 14 participants (actual)
Lead sponsor: Vanda PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: May 2014
Primary completion: May 2014 (actual)
Study completion: May 2014 (actual)
First posted: 6 May 2014 (estimated)
Results: Posted 22 Jul 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Sequence A	Experimental	Drug: tasimelteon 20 mg capsule, Drug: tasimelteon 2 mg I.V.* Single oral dose of tasimelteon 20 mg on Day 1 * Single I.V. dose of tasimelteon 2 mg on Day 6
Sequence B	Experimental	Drug: tasimelteon 20 mg capsule, Drug: tasimelteon 2 mg I.V.* Single I.V. dose of tasimelteon 2 mg on Day 1 * Single oral dose of tasimelteon 20 mg on Day 6

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (12 listed)

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:

Key exclusion criteria (21 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
tasimelteon 20 mg capsuleAlso: Hetlioz™ 20 mg	Drug	Sequence A, Sequence B
tasimelteon 2 mg I.V.	Drug	Sequence A, Sequence B

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.

8 secondary outcomes

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
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
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
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
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
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
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
Number of Participants With Adverse Events
Time frame: From Baseline to End of Study; Day 5 (± 2 days).

Results and safety

Results posted to the registry on 22 Jul 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Sequence A	6	6
Sequence B	8	8

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. Geometric mean (90% Confidence Interval). Unit: Geometric Mean Ratio (%)

Measure	Absolute Bioavailability n = 14
Value	38.3 (26.9 to 54.3)

8 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Tasimelteon 20mg Oral	0 of 14 (0%)	2 of 14 (14.3%)	Not reported
Tasimelteon 2mg IV	0 of 14 (0%)	1 of 14 (7.1%)	Not reported
All Subjects	0 of 14 (0%)	3 of 14 (21.4%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing tasimelteon 20 mg capsule and tasimelteon 2 mg I.V. in people with Non-24-Hour-Sleep-Wake Disorder, run by Vanda Pharmaceuticals.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Jul 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02130999.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2016.