A multicenter, double-blind, randomized study to evaluate the effects of tasimelteon vs. placebo in participants with Delayed Sleep-Wake Phase Disorder (DSWPD)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vanda Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

23 Sep 2022 → ongoing

Decision date (initial)

2024-11-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Vanda Pharmaceuticals, Inc.

External identifiers

EU CT number

2024-516962-13-00

EudraCT number

2021-005475-40

ClinicalTrials.gov

NCT04652882

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacogenetic, Safety, Therapy

To assess the effects of a daily single oral dose of 20 mg tasimelteon compared to placebo on Sleep Onset (change from baseline) in participants over a 28-day period, as measured by sleep diary.

Secondary objectives 9

1. To assess the effects of 20 mg tasimelteon compared to placebo on Sleep Onset (change from baseline) during the treatment phase, as measured by actigraphy.
2. To assess the effects of 20 mg tasimelteon compared to placebo on nighttime subjective sleep parameters such as sleep onset latency (SOL), wake time, midpoint of sleep, and total sleep time (change from baseline), as measured by sleep diary.
3. To assess the effects of 20 mg tasimelteon compared to placebo on nighttime objective sleep parameters such as SOL, wake time, midpoint of sleep, and total sleep time (change from baseline), as measured by actigraphy.
4. To assess the effects of 20 mg tasimelteon compared to placebo on subjective sleep-related impairments and subjective sleep disturbances, as measured by the Patient- Reported Outcomes Measurement Information System (PROMIS).
5. To assess the effects of 20 mg tasimelteon compared to placebo on global improvement and severity, as measured by Clinical Global Impression of Change (CGI-C), Patient Global Impression of Change (PGI-C), and Patient Global Impression of Severity (PGI-S).
6. To assess the effects of 20 mg tasimelteon compared to placebo on the change in circadian phase from baseline to post-treatment, as measured by salivary Dim Light Melatonin Onset (DLMO).
7. To assess the effects of 20 mg tasimelteon on Sleep Onset (change from baseline) in participants with delayed DLMO compared to participants with non-delayed DLMO, as measured by sleep diary.
8. To assess the effects of 20 mg tasimelteon on Sleep Onset (change from baseline) in participants with PER3 rs57875989 (specifically genotype 4/4 and 4/4+4/5), as measured by sleep diary.
9. To assess the safety and tolerability of a daily single oral dose of 20 mg tasimelteon.

Conditions and MedDRA coding

Delayed Sleep-Wake Phase Disorder (DSWPD)

Study design 4 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Ability and acceptance to provide written informed consent.
2. A confirmed clinical diagnosis of DSWPD, as per International Classification of Sleep Disorders-3 (ICSD-3).
3. Males or females between 18 – 75 years, inclusive.
4. Body Mass Index (BMI) of ≥ 18 and ≤ 35 kg/m2 (BMI = weight (kg)/[height (m)]2).
5. Males, non-fecund females (i.e., surgically sterilized, if procedure was done 6 months before screening or participant is postmenopausal for at least 2 years), or females of childbearing potential using an acceptable method of birth control (abstinence, the use of 2 independent barrier methods, hormonal contraception plus 1 barrier method, or surgically sterilized partner) for a period of 35 days before the first dosing, and agree to continue using these methods during the study, and for one month after the last dose. Women of Childbearing Potential (WOCBP) must also have a negative pregnancy test at V1, V2, and V3.
6. In good health as determined by a medical history, physical examination, electrocardiogram (ECG), serum chemistry and hematology, and urinalysis.
7. Willing to comply with study procedures and restrictions with fixed sleep time during the study and to attend regularly scheduled clinic visits as specified in the protocol.
8. Must have a desired bedtime at least 2 hours earlier than the habitual sleep onset (determined by the DSPD Screening Questionnaire). There must be at least a 2 hour difference between the reported sleep onset, by daily sleep diary, and the desired bedtime (determined by the DSPD Screening Questionnaire), on at least 5 of the 7 days per screening week.
9. Must have a sleep onset of 00:00 or later (determined by the DSPD Screening Questionnaire).
10. Must have a reported sleep onset of 00:00 or later by daily sleep diary, on at least 5 of the 7 days per screening week.
11. Must have 80% compliance for daily sleep diary completion, throughout screening.
12. Must maintain an actual bedtime ± 15 minutes from the desired bedtime by daily sleep diary, on at least 5 of the 7 days during the run-in.
13. Must have a reported sleep onset of ≥ 2 hours from the desired bedtime by daily sleep diary, on at least 5 of the 7 days during the run-in.

Exclusion criteria 26

1. Current clinically significant cardiovascular, respiratory, neurologic, hepatic, hematopoietic, renal, gastrointestinal, or metabolic dysfunction unless currently controlled and stable.
2. Acute exacerbation of an existing psychiatric comorbid condition that requires change in treatment or intervention in the 3 months prior to the screening visit.
3. History of intolerance and/or hypersensitivity to melatonin or melatonin agonists.
4. Indication of impaired liver function (values for enzymes aspartate transaminase (AST) and alanine transaminase (ALT) or bilirubin > 2 times the Upper Limit of Normal).
5. Clinically significant deviation from normal in clinical laboratory results, vital sign measurements, or physical examination findings as determined by the Investigator.
6. Major surgery, trauma (including broken pelvis/legs), illness (i.e., sepsis, stroke), general anesthesia, or immobility for 3 or more days within 30 days of the screening visit.
7. Current tobacco user or quit using tobacco within 30 days of the screening visit.
8. Active cancer or cancer treatment within 6 months of the screening visit.
9. Central venous catheter in place or within 30 days of the screening visit.
10. Recent history of pulmonary embolism/deep vein thrombosis (DVT) or short-term blood thinner treatment as an outpatient (i.e., Coumadin, Lovenox, Heparin), one year prior to the screening visit.
11. Recent history or family history of thrombosis or hypercoagulable state (i.e., Factor V Leiden, Factor VIII deficiency, Protein C & S deficiency), one year prior to the screening visit.
12. Pregnancy, recent pregnancy (within 6 weeks of the screening visit), or females who are breastfeeding.
13. History of restless leg syndrome, sleep apnea, or periodic limb movement disorder and/or have current diagnosis as confirmed by the screening visit.
14. History or evidence of sleep apnea as determined by a high-risk score in any two of the three categories in The Berlin Questionnaire (TBQ), unless ruled out by a recent sleep study for sleep apnea.
15. History of drug or alcohol abuse as defined in DSM-V, Diagnostic Criteria for Drug and Alcohol Abuse, within the 12 months prior to screening and/or regular consumption of alcoholic drinks (> 2 drinks/day or > 14 drinks/week).
16. A positive test for substances of abuse at the screening visit, V2, or V3.
17. Traveled more than 3 time zones 2 weeks prior to the screening visit.
18. Traveled outside the origination time zone within 1 week before the screening period and until the end of the treatment period.
19. Worked regular night shifts in the 2 months leading up to the screening visit.
20. Randomization in a previous tasimelteon (VEC-162 or BMS-214778) trial.
21. Use of any investigational drug, including placebo, any central nervous system medication (unless on a chronic, stable dose of the medication), or any other prescription or over-the-counter (OTC) medication that affects the sleep-wake cycle within 3 weeks or 5 half-lives (whichever is longer) of the screening visit.
22. Participant is at risk of suicide, in the opinion of the Investigator. Evidence of suicide risk could include any suicide attempt or any other suicidal behavior within 12 months of the screening visit or any suicidal ideation of type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) at V1, V2, or V3.
23. Unwilling or unable to follow the medication restrictions, or unwilling or unable to sufficiently washout from use of a restricted medication.
24. Use of melatonin or melatonin agonist within 3 weeks of the screening visit.
25. Have a reported change of ≥ 2 hours from the average reported sleep onset from screening by daily sleep diary, during the run-in.
26. Any other sound medical reason as determined by the Investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To assess the effects of a daily single oral dose of 20 mg tasimelteon compared to placebo on Sleep Onset (change from baseline) in participants over a 28-day period, as measured by sleep diary.

Secondary endpoints 9

1. To assess the effects of 20 mg tasimelteon compared to placebo on Sleep Onset (change from baseline) during the treatment phase, as measured by actigraphy.
2. To assess the effects of 20 mg tasimelteon compared to placebo on nighttime subjective sleep parameters such as SOL, wake time, midpoint of sleep, and total sleep time (change from baseline), as measured by sleep diary.
3. To assess the effects of 20 mg tasimelteon compared to placebo on nighttime objective sleep parameters such as SOL, wake time, midpoint of sleep, and total sleep time (change from baseline), as measured by actigraphy.
4. To assess the effects of 20 mg tasimelteon compared to placebo on subjective sleep-related impairments and subjective sleep disturbances, as measured by PROMIS.
5. To assess the effects of 20 mg tasimelteon compared to placebo on global improvement and severity, as measured by CGI-C, PGI-C, and PGI-S.
6. To assess the effects of 20 mg tasimelteon compared to placebo on the change in circadian phase from baseline to post-treatment, as measured by salivary DLMO.
7. To assess the effects of 20 mg tasimelteon on Sleep Onset (change from baseline) in participants with delayed DLMO compared to participants with non-delayed DLMO, as measured by sleep diary.
8. To assess the effects of 20 mg tasimelteon on Sleep Onset (change from baseline) in participants with PER3 rs57875989 (specifically genotype 4/4 and 4/4+4/5), as measured by sleep diary.
9. To assess the safety and tolerability of a daily single oral dose of 20 mg tasimelteon.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vanda Pharmaceuticals Inc.

Sponsor organisation

Vanda Pharmaceuticals Inc.

Address

2200 Pennsylvania Avenue Northwest Suite 300

City

Washington

Postcode

20037-1709

Country

United States

Scientific contact point

Organisation

Vanda Pharmaceuticals Inc.

Contact name

Christos Polymeropoulos

Public contact point

Organisation

Vanda Pharmaceuticals Inc.

Contact name

Christos Polymeropoulos

Third parties 1

Locations

2 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 58 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications