Four-week Study of the Safety and Efficacy of NLS-2 (Mazindol Extended Release) in the Treatment of Narcolepsy

Study Overview
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Brief Summary
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This is a double-blind, randomized, placebo-controlled, multicenter trial of NLS-2 in adult patients with narcolepsy. The study will enroll approximately 60 patients and eligible patients will be treated to receive either NLS-2 or placebo for 4-weeks.

Official Title
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A Four-week, Double-blind, Placebo-controlled, Randomized, Multicenter, Parallel-group Study of the Safety and Efficacy of NLS-2 (Mazindol Extended Release) in Adults for the Treatment of Narcolepsy

Conditions
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Narcolepsy, Excessive Daytime Sleepiness, Cataplexy Narcolepsy

Intervention / Treatment
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* Drug: mazindol extended release
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Males and females between 18 and 65 years of age, inclusive Diagnosis of narcolepsy according to ICSD-3 (International Classification of Sleep Disorders, 3rd Edition) or Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria Body mass index from 18 to 40 kg/m2, inclusive Consent to use a medically acceptable method of contraception Willing and able to provide written informed consent Key Exclusion Criteria: Female subjects who are pregnant, nursing, or lactating Any other clinically relevant medical, behavioral, or psychiatric disorder other than narcolepsy that is associated with excessive sleepiness History or presence of bipolar disorder, bipolar related disorders, schizophrenia, schizophrenia spectrum disorders, or other psychotic disorders according to DSM-5 criteria Use of any over-the-counter (OTC) or prescription medications that could affect the evaluation of excessive sleepiness Use of any medications that could affect the evaluation of cataplexy Received an investigational drug in the past 30 days or five half-lives (whichever is longer)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: NLS-2 (mazindol extended release)<br>2 mg dosed orally, once daily for 1 week; followed by 3 mg dosed orally, once daily for up to 3 weeks (total of 4 weeks) | Drug: mazindol extended release<br>* Dosed orally, once daily for up to 3 weeks<br>* Other names: NLS-2;|
| Placebo Comparator: Placebo<br>Dosed orally, once daily for up to 4 weeks | Drug: Placebo<br>* Dosed orally, once daily for up to 4 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ESS Score From Baseline to Week 4 | Change in Epworth Sleepiness Scale (ESS) score from Baseline to Week 4. A negative change from baseline represents improvement in excessive sleepiness. The ESS is a self-administered questionnaire with 8 questions. Each activity is scored on a scale ranging from 0-3, with 0 = would never fall asleep, and 3 = high chance of falling asleep. The total score ranges from 0-24, with a higher number representing an increased propensity for sleepiness. | Baseline to Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjects Reported Improved on the Patient Global Impression of Change (PGIc) at Week 4 | Percentage of subjects reported as improved (minimally, much, or very much) on the PGIc at Week 4. PGIc is rated by subjects and measures the change in their condition since treatment starts on a 7-point scale ranging from 1= very much improved to 7= very much worse | Baseline to Week 4 |