Trial document




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  DRKS00003187

Trial Description

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Title

A MULTICENTER, RANDOMIZED, DOUBLE-MASK, PLACEBO-CONTROLLED, PARALLEL STUDY TO INVESTIGATE THE EFFICACY AND SAFETY OF 20 MG TASIMELTEON VERSUS PLACEBO IN TOTALLY BLIND SUBJECTS WITH N24HSWD FOLLOWED BY AN OLE PHASE

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Trial Acronym

VP-VEC-162-3201

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URL of the Trial

http://www.vandapharma.com

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Brief Summary in Lay Language

Clinical Study to evaluate an investigational new medicine for a condition called Non-24-Hour Sleep-Wake Disorder. This clinical study is looking for individuals who are totally blind and who experience a cyclical problem with being able to sleep at night and daytime sleepiness during the day. Symptoms, which include severe insomnia, sleep deprivation, and sleepiness during the day usually occur for a few weeks to months and may seem to go away only to return again. This problem may be caused by the lack of the signal that light usually provides to the body to regulate sleeping and waking. The result is recurrent sleep problems similar to jet lag.

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Brief Summary in Scientific Language

This will be a multicenter, randomized, double-masked, placebo-controlled, parallel study. The study has three phases: the pre-randomization phase, the randomization phase, and the open-label extension. The pre-randomization phase comprises a screening visit where subject’s initial eligibility will be evaluated, a circadian period (, tau) estimation segment, and a variable-length in-phase transition segment in which subjects will wait to start treatment until their circadian phase is aligned with their target bedtime. Subjects that meet all entry criteria for the study will enter the randomization phase. The randomization phase comprises the evaluation segment and the washout segment. During the evaluation segment, subjects will be asked to take either 20 mg tasimelteon or placebo approximately 1 hour prior to their target bedtime for 26 weeks in a double-masked fashion. During the washout segment, subjects will be treated for 2-weeks with placebo in a single-masked fashion. Subjects that complete this phase of the study will be given the opportunity to participate in the optional open-label extension (OLE) phase. Additionally, subjects who have a tau greater than 24.0 and meet all entry criteria but that are ineligible for the randomization phase due to their tau estimate will be given the opportunity to participate in the OLE phase. During the OLE phase, subjects will take open-label 20mg tasimelteon for 26 weeks.

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Organizational Data

  •   DRKS00003187
  •   2011/07/21
  •   2010/07/02
  •   no
  •   Approved
  •   PVN3752, Ethik-Kommission der Ärztekammer Hamburg
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Secondary IDs

  •   2011-000281-35 
  •   NCT01163032  (ClinicalTrials.gov)
  •   4037148 
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Health Condition or Problem studied

  •   Non-24 Hour Sleep Wake Disorder
  •   G47.2 -  Disorders of the sleep-wake schedule
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Interventions/Observational Groups

  •   Tasimelteon will be administered orally as a dose of 20 mg. All capsules will be size 1 and the color will be dark blue with a white stripe printed on both the cap and body of the capsule.
    Duration of treatment:
    Up to 26 weeks (initial double-masked phase); Up to 54 weeks total (including open-label extension)
  •   Placebo capsules will be provided in size and appearance identical to those containing tasimelteon and will be administered orally over a time period up to 26 weeks
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Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Double or multiple blind
  •   [---]*
  •   Placebo
  •   Other
  •   Parallel
  •   III
  •   [---]*
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Primary Outcome

To determine the efficacy of tasimelteon in improving subjective nighttime total sleep time (nTST) in subjects with N24HSWD as measured by daily Post-Sleep Questionnaires (PSQs).

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Secondary Outcome

Efficacy:
1. To determine the efficacy of tasimelteon in reducing total daytime sleep duration in subjects with N24HSWD.
2. To assess tasimelteon’s effect on the circadian melatonin rhythm.
3. To assess the effects of tasimelteon to treat N24HSWD as measured by a Clinical Global Impression of Change (CGI-C).
Safety:
1. To assess the potential for withdrawal symptoms after the abrupt discontinuation of tasimelteon during a two week placebo washout period.
2. To assess the potential for post-treatment effects immediately (during 3 days) after the abrupt discontinuation of tasimelteon.
3. To explore the safety and tolerability of multiple oral doses of tasimelteon.
4. To assess the effect of tasimelteon on measures of endocrine function.

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Countries of Recruitment

  •   United States
  •   Germany
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Locations of Recruitment

  • [---]*
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Recruitment

  •   Actual
  •   2011/08/08
  •   84
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   75   Years
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Additional Inclusion Criteria

Ability and acceptance to provide informed consent; Men or women between 18-75 years of age, inclusive; Body Mass Index (BMI) of ≥ 18 and ≤ 33 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 1 year before screening), or females of child-bearing potential using 2 independent barrier methods of birth control (i.e., condoms, diaphragm, spermicidal agents, cervical cap) for a period of 35 days before the first dosing, during the study and for one month after the last dose and must have a negative pregnancy test at the screening and baseline visits;
Note: Hormonal contraception is not considered a reliable method of birth control in this study.
Note: For patients over 55 years of age at the screening visit absence of menses for 1 year before screening is sufficient to establish the postmenopausal status. The postmenopausal status of a patient under 55 years of age at the screening visit will be confirmed by measuring the following hormones:
Follicle-stimulating hormone (FSH) ≥ 40 mIU/mL
Estradiol ≤ 30 pg/mL (110.1 pmol/L); Willing to comply with study requirements and restrictions including commitment to a fixed 9-hour sleep opportunity during the study; Fluent in English or German, for US and German participants, respectively; No perception of light; Tau length of ≥ 24.25 and the lower bound of 95% CI > 24.1 and the upper bound of 95% CI < 24.9 based on urinary aMT6s rhythms;
Diagnosis of N24HSWD as determined by: History (within the last 3 months) of trouble sleeping at night (difficulty initiating sleep or staying asleep), difficulty awakening in the morning, or daytime sleepiness as determined by answering yes to at least one question in the Sleep Complaint Questionnaire and
urinary aMT6s demonstrates a progressive delay of the aMT6 acrophase time.

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Exclusion Criteria

Subjects will be excluded from the study if any of the following criteria apply:
Have a probable diagnosis of a current sleep disorder other than N24HSWD that is the primary cause of the sleep disturbance based on clinical investigator medical judgment; History (within the 12 months prior to screening) of psychiatric disorders including Major Depressive Disorder, Generalized Anxiety Disorder, Axis II Disorders, delirium or any other psychiatric disorder, that is not being successfully treated or has not been resolved and that in the opinion of the clinical investigator would affect participation in the study or full compliance with study procedures;
Subjects who take NSAIDs daily and would not interrupt their use for the study;
History of intolerance and/or hypersensitivity to melatonin or melatonin agonists;
History of drug or alcohol abuse as defined in DSM-IV, 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);
a.Note: A standard drink is equal to 13.7 grams (0.6 ounces) of pure alcohol or
o 12-ounces of beer
o 8-ounces of malt liquor
o 5-ounces of wine
o 1.5-ounces or a “shot” of 80-proof distilled spirits or liquor (e.g., gin, rum, vodka, or whiskey);
Subjects having any suicidal ideation of type 4 or 5 on the C-SSRS at Screening or Baseline; Subject is at risk of suicide, in the opinion of the Investigator. Evidence of suicide risk could include any suicide attempt within the past year or any other suicidal behavior within the past year;
Current clinically significant cardiovascular, respiratory, neurologic, hepatic, hematopoietic, renal, gastrointestinal or metabolic dysfunction unless currently controlled and stable;
Subjects who have estimated creatinine clearance (CLcr; based on the Cockcroft-Gault equation) ≤ to 55 mL/min;
Clinically significant deviation from normal in clinical laboratory results, vital signs measurements, or physical examination findings at screening as determined by the clinical investigator;
Indication of impaired liver function (values for AST, ALT or bilirubin > 2 times Upper Limit of Normal); Pregnant or lactating females; A positive test for drugs of abuse at the screening visit;
Note: A positive drug screen at Visit 1 needs to be discussed with the medical monitor and will be evaluated on a case-by-case basis. Smoke more than 10 cigarettes/day; Worked night, rotating, or split (period of work, followed by break, and then return to work) shift work within 1 month of the screening visit or plan to work these shifts during the study; Participation in a previous tasimelteon (aka VEC-162 or BMS-214778) trial; Exposure to any investigational drug, including placebo, within 30 days or 5 half-lives (whichever was longer) of screening; Unwilling or unable to follow the medication restrictions described in Section 8.2., or unwilling or unable to sufficiently wash-out from use of a restricted medication; Use of melatonin or melatonin agonist within 1 week of the tau identification segment; Unable to perform calls to the study IVR system to report questionnaire results; Any other sound medical reason as determined by the clinical investigator; Legal incompetence or limited legal competence, detainment in an institution for official or legal reasons.

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Addresses

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    • Vanda Pharmaceuticals Inc.
    • 9605 Medical Center Drive Suite 300
    • MD 20850  Rockville
    • United States
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    •   +1 240.599.4500
    •   [---]*
    •   [---]*
    •   [---]*
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    • Vanda Pharmaceuticals Inc.
    • Mr.  Dr.  John  Feeney 
    • 2200 Pennsylvania Avenue NW, Suite 300-E
    • DC 20037  Washington
    • United States
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    • Vanda Pharmaceuticals Inc.
    • Ms.  Cristina  Murphy 
    • 2200 Pennsylvania Avenue NW
    • DC 20037  Washington
    • United States
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Sources of Monetary or Material Support

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    • Vanda Pharmaceuticals Inc.
    • 2200 Pennsylvania Avenue NW, Suite 300-E
    • DC 20037  Washington
    • United States
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    •   +1 202.734.3400
    •   [---]*
    •   [---]*
    •   [---]*
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Status

  •   Recruiting complete, follow-up complete
  •   2012/10/29
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.