Cataplexy, EDS, Fatigue, Narcolepsy
Conditions
Keywords
pitolisant, HBS-301, narcolepsy, EDS, cataplexy, fatigue
Brief summary
This is a Phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled clinical study to assess the efficacy and safety of HBS-301 in treating excessive daytime sleepiness (EDS), cataplexy, sleepiness/wakefulness, and fatigue in adult participants (ages ≥18 years) with narcolepsy.
Detailed description
This is a Phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled clinical study to assess the efficacy and safety of HBS-301 in treating EDS, cataplexy, sleepiness/wakefulness, and fatigue in adult participants (ages ≥18 years) with narcolepsy. Approximately 258 participants are planned for randomization into the study. The study will consist of a Screening/Baseline Period (up to 28 days), a Double-blind Treatment Period (8 weeks), an optional Open-label Extension Period (1 year), and 30 days of safety follow-up.
Interventions
DRUGHBS-301
HBS-301 tablet
OTHERPlacebo
Placebo tablet
Sponsors
Harmony Biosciences Management, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has a current documented diagnosis of NT1 or NT2 per the International Classification of Sleep Disorders, Third Edition (ICSD-3) or the ICSD-3 Text Revision (ICSD-3-TR) within the last 10 years. * Has EDS. * If taking a permitted chronic concomitant medication or supplement, including nonprohibited antidepressants or wake-promoting agents, must be on a stable dose for at least 3 months prior to Screening and agree to continue at that stable dose for the Double-blind Treatment Period of the study. As needed (PRN) use of any treatment that could affect daytime sleepiness (including but not limited to oxybates, stimulants, modafinil, and armodafinil) is not permitted.
Exclusion criteria
* Has hypersomnia due to another medical disorder. * Has a history of pitolisant use within 5 half-lives prior to Screening. * Has a primary diagnosis of psychiatric illness, including depression, that is not well controlled (i.e., symptoms and medications have not been stable for at least 3 months prior to Screening). * Has any history of bipolar disorder or psychosis * Has acute or chronic liver disease or a history of moderate or severe hepatic impairment. * Has a body surface area-corrected estimated glomerular filtration rate (eGFR) \<60 mL/min. * Has a known history of long QT syndrome or serious abnormality of the electrocardiogram (ECG).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in severity of EDS as measured by the Epworth Sleepiness Scale (ESS) | Baseline to end of Double-Blind Treatment Period (8 weeks) | The ESS is an 8-item, 4-point rating scale. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in health-related quality of life as measured by the Short Form-36 physical and mental component summaries | Baseline to the end of the Double-blind Treatment Period (8 weeks) | The Short Form-36 includes 36 questions across 8 health domains to measure a participant's functional health and well-being. |
| Change in work productivity as measured by the Work Productivity and Activity Impairment: Narcolepsy work productivity loss score | Baseline to the end of the Double-blind Treatment Period (8 weeks) | The Work Productivity and Activity Impairment: Narcolepsy questionnaire is a 6-item scale used to measure impairments over 7 days. |
| Incidence of treatment-emergent adverse events | Throughout study (16 months, including Open-label Extension) | A treatment-emergent adverse event is any adverse event reported after the first dose of study drug and up to 30 days after final dose of study drug, or any worsening of a pre-existing condition reported after first dose of study drug and up to 30 days after final dose of study drug. |
| Evaluate the pharmacokinetic concentrations of pitolisant and major identified metabolites | Throughout study (16 weeks) | Pharmacokinetics is the study of how the body interacts with administered substances for the duration of exposure. |
| Change in Weekly Rate of Cataplexy (WRC) in participants with an average WRC of ≥3 over 2 consecutive weeks at Screening | End of the Double-Blind Treatment Period (8 weeks) | The WRC is the average number of cataplexy attacks per week. |
| Change in sleepiness/wakefulness measured by the Maintenance of Wakefulness Test (MWT) | Baseline to the end of the Double-blind Treatment Period (8 weeks) | The MWT consists of a series of 20-minute to 40-minute trials spaced 2 hours apart and is used to measure an individual's ability to stay awake. |
| Change in fatigue as measured by the Patient-Reported Outcomes Measurement Information System Fatigue Short Form 7a (PROMIS-Fatigue-SF-7a) | Baseline to end of Double-Blind Treatment Period (8 weeks) | The PROMIS-Fatigue-SF-7a is a 7-question, 5-point scale used to assess fatigue. |
| Change in severity of EDS as measured by the ESS | Baseline through Week 1 and through Week 2 of Titration Period (1 week and 2 weeks) | The ESS is an 8-item, 4-point rating scale. |
| Onset of efficacy of HBS-301 compared with placebo in treating cataplexy measured by WRC in participants with an average WRC of ≥3 over 2 consecutive weeks during Screening | Baseline through Week 1 and Week 2 of the Titration Period (1 week and 2 weeks) | The WRC is the average number of cataplexy attacks per week. |
| Change in severity of EDS as measured by the Clinical Global Impression of Change (EDS) | Baseline to end of Double-blind Treatment Period (8 weeks) | The Clinical Global Impression of Change (EDS) is a 7-point scale used to measure the improvement or worsening of the participant's EDS relative to a baseline. |
| Change in severity of EDS as measured by the Patient Global Impression of Severity (EDS) | Time Frame: Baseline to the end of the Double-blind Treatment Period (8 weeks) | The Patient Global Impression of Severity (EDS) is a participant-reported assessment that gauges the severity of a participant's EDS symptoms. |
| Improvement in the severity of EDS as measured by the Patient Global Impression of Change (EDS) | Baseline to the end of the Double-blind Treatment Period (8 weeks) | The Patient Global Impression of Change (EDS) is a participant-reported outcome used to evaluate the effectiveness of a treatment on their EDS symptoms. |
| Change in severity of cataplexy as measured by the Clinical Global Impression of Severity (Cataplexy) in participants with an average WRC of ≥3 over 2 consecutive weeks during Screening | Baseline to the end of the Double-blind Treatment Period (8 weeks) | The Clinical Global Impression of Severity (Cataplexy) is a 3-item observer-rated scale used to track cataplexy symptom changes. |
| Change in severity of cataplexy as measured by the Patient Global Impression of Severity (Cataplexy) in participants with an average WRC of ≥3 over 2 consecutive weeks during Screening | Baseline to the end of the Double-blind Treatment Period (8 weeks) | The Patient Global Impression of Severity (Cataplexy) is a participant-reported assessment that gauges the severity of cataplexy symptoms. |
| Improvement in severity of cataplexy as measured by the Patient Global Impression of Change (Cataplexy) in participants with an average WRC of ≥3 over 2 consecutive weeks during Screening | Baseline to the end of the Double-blind Treatment Period (8 weeks) | The Patient Global Impression of Change (Cataplexy) is a participant-reported outcome used to evaluate the effectiveness of a treatment on their cataplexy symptoms. |
| Change in severity of fatigue as measured by the Patient Global Impression of Severity (Fatigue) | Baseline to the end of Double-blind Treatment Period (8 weeks) | The Patient Global Impression of Severity (Fatigue) is a participant-reported assessment that gauges the severity of a participant's fatigue symptoms. |
| Change in severity of fatigue as measured by the Patient Global Impression of Change (Fatigue) | Baseline to the end of the Double-blind Treatment Period (8 weeks) | The Patient Global Impression of Change (Fatigue) is a participant-reported outcome used to evaluate the effectiveness of a treatment on their fatigue symptoms. |
| Change in cognitive complaints as measured by the British Columbia Cognitive Complaints Inventory | Baseline to the end of the Double-blind Treatment Period (8 weeks) | The British Columbia Cognitive Complaints Inventory is a participant-reported, 6-item, 4-point scale that assesses perceived cognitive difficulties. |
| Change in severity of narcolepsy symptoms as measured by the Narcolepsy Severity Scale (for participants with NT1) or Narcolepsy Severity Scale-2 (for participants with NT2) | Baseline to the end of the Double-blind Treatment Period (8 weeks) | The Narcolepsy Severity Scale is a 15-item participant-reported questionnaire that assesses the severity and consequences of narcolepsy symptoms. |
Countries
Canada, United States
Contacts
CONTACTMichelle Manuel
CONTACTKatie Wilmsen
STUDY_DIRECTORDavid Seiden, MD
Harmony Biosciences Management, Inc.
Outcome results
None listed