Idiopathic Hypersomnia, Narcolepsy
Conditions
Keywords
Idiopathic Hypersomnia, Narcolepsy, Excessive daytime sleepiness, Polysomnography, JZP258, XYWAV, Oxybate
Brief summary
This study will assess the safety and efficacy of JZP258 (XYWAV) on sleepiness, polysomnography, and functional outcomes in patients with idiopathic hypersomnia (IH) or narcolepsy.
Detailed description
This prospective, multicenter, single-arm, open-label interventional study will assess the safety and efficacy of JZP258 on sleepiness, polysomnography measurements (eg, sleep stage transitions, sleep patterns, and sleep quality), daytime and nighttime symptoms, pharmacokinetics (in narcolepsy), and patient-reported outcomes that include subjective sleep quality and quality of life in patients with IH or narcolepsy.
Interventions
DRUGJZP258 (XYWAV)
Narcolepsy Cohort: Initiate dosage per XYWAV label and titrate to effect. IH Cohort: Initiate dosage per XYWAV label and titrate to effect. Exploratory Narcolepsy \>9-Gram Cohort: XYWAV titrated to a dosage of \>9 to 12 grams.
Sponsors
Jazz Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Is 18 to 75 years of age (inclusive) at the time of signing the informed consent form (ICF) * Has a primary diagnosis of IH meeting International Classification of Sleep Disorders, Third Edition (ICSD-3) criteria or narcolepsy (Type 1 or Type 2) meeting ICSD-3 or Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria. * If not currently taking oxybate medication, has clinically significant symptoms of Excessive daytime sleepiness (EDS) with an ESS score \> 10 at Screening Visit 1. If currently taking oxybate medication, has an ESS score \> 10 at the Baseline Visit 2 polysomnography (after washout period). Note: Not applicable for participants entering the Narcolepsy \>9-gram cohort (see additional criteria below for the Narcolepsy \>9-gram cohort). * If currently treated with anticataplectics and/or alerting agents, has been taking the same dosage for at least 1 month prior to Screening Visit 1 and has no current plans to adjust the dosage during the study period. Note: Alerting agents refer to either traditional stimulants (eg, amphetamines, methylphenidates) or wake-promoting agents (eg, modafinil, pitolisant, solriamfetol). Additional Inclusion Criteria for Participants in the Exploratory Narcolepsy \>9-Gram Cohort * Is on a current treatment regimen including XYWAV at a dosage of 9 grams Key
Exclusion criteria
* Shows evidence of a previous untreated or inadequately treated sleep disorder considered by the investigator to negatively impact the conduct of the study, including sleep-disordered breathing, parasomnias, circadian rhythm sleep disorders, or restless legs syndrome determined by a previous sleep-laboratory diagnosis or interview utilizing modules of the Diagnostic Interview for Sleep Patterns and Disorders. * Shows evidence of untreated or inadequately treated sleep-disordered breathing during Baseline Visit 2 polysomnography defined as an Apnea/Hypopnea Index (AHI) \> 10, using the US Centers for Medicare and Medicaid Services rules (CMS.gov). * Has a history or presence of any unstable or clinically significant medical condition (chronic pain condition that may impact sleep), behavioral or psychiatric disorder (including active suicidal ideation or current or past \[within 1 year\] major depressive episode), or history or presence of another neurologic disorder or surgical history that might affect the participant's safety and/or interfere with the conduct of the study, in the opinion of the investigator. * Has recently taken (ie, within 1 month prior to screening), is taking, or plans to take any of the following: * A substance or medication contraindicated with XYWAV use, ie. specifically alcohol and sedative hypnotics * A medication with a known drug-drug interaction with XYWAV * A medication that may have similar EEG effects to XYWAV * Medications known to have clinically significant CNS sedative effects * Other medications, natural health products, or substances from which the participant experiences clinically significant sedation Additional Exclusion Criterion for Participants in the Exploratory Narcolepsy \>9-Gram Cohort • Any past or current medical conditions or experience that, in the investigator's clinical judgment, would preclude further increases in the current oxybate medication dosage beyond 9 grams
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score in Participants With IH and Narcolepsy Treated With XYWAV | Baseline up to End of Treatment (approximately 10-36 weeks) | The ESS total score (the sum of 8 item scores, each 0 to 3) can range from 0 to 24. Higher ESS total scores are associated with higher sleep propensity in daily life, also referred to as "daytime sleepiness." |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Idiopathic Hypersomnia Severity Scale (IHSS) Total Score in Participants With IH Treated With XYWAV | Baseline up to End of Treatment (approximately 10-21 weeks) | The IHSS is a 14-item self-reported instrument that assesses the severity and functional consequences of IH symptoms. Questions capture symptoms of excessive sleepiness, sleep inertia, and long sleep duration. IHSS total scores range from 0 to 50 with higher score indicating worse clinical outcome. |
| Change From Baseline in Number of Stage Shifts of Sleep in Participants With Narcolepsy Treated With XYWAV | Baseline up to End of Treatment (approximately 10-36 weeks) | Stage shifts of sleep are defined as the count of transitions of bouts of sleep from deeper to lighter stages of sleep/wake (ie from N3/N2/N1/REM to wake and from N3/N2/REM to N1). |
| Change From Baseline in Duration of Sleep Stages in Participants With Narcolepsy Treated With XYWAV | Baseline up to End of Treatment (approximately 10-36 weeks) | Duration of sleep stages is measured in minutes (ie N1/N2/N3/REM) and is recorded from sleep onset to awakening during the nocturnal polysomnograph. |
| Change From Baseline in Number of Nocturnal Awakenings and Nocturnal Arousals in Participants With Narcolepsy Treated With XYWAV | Baseline up to End of Treatment (approximately 10-36 weeks) | — |
| Change From Baseline in Percentage of Sleep Stages in Participants With Narcolepsy Treated With XYWAV | Baseline up to End of Treatment (approximately 10-36 weeks) | The percentage of sleep stages is measured as minutes of each sleep stage (N3/N2/N1/REM) per hour of sleep time from sleep onset to awakening in the nocturnal polysomnograph. |
| Patient Global Impression of Change (PGI-C) in Participants With IH and Narcolepsy Treated With XYWAV (Overall, Sleep Inertia, and Fatigue) | End of Treatment (approximately 10-36 weeks) | The PGI-C is a single-item 7-point, Likert-type scale for rating change in disease or symptom severity. Responses for each question ranged from 1 (very much improved) to 7 (very much worse) relative to baseline. Participants rated the change from baseline in their overall (IH or narcolepsy) symptoms, sleep inertia (difficulty waking in the morning), and fatigue (extreme tiredness resulting from mental or physical exertion). |
| Level of Rested or Refreshed Upon Awakening in Participants With IH and Narcolepsy Treated With XYWAV (Sleep Diary) | Baseline up to End of Treatment (approximately 10-36 weeks) | The participant was asked "How rested or refreshed did you feel when you woke up for the day?" |
| Patient Global Impression of Severity (PGI-S) Score in Participants With IH and Narcolepsy Treated With XYWAV (Overall, Sleep Inertia, and Fatigue) | Baseline up to End of Treatment (approximately 10-36 weeks) | The PGI-S is a single-item, 7-point, Likert-type scale for rating disease or symptom severity. Responses ranged from 0 (not present) to 7 (extremely severe). Participants rated the severity of their overall (IH or narcolepsy) symptoms, sleep inertia, and fatigue. Higher scores indicate worse clinical outcome. |
| Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) In a Subset of Participants With Narcolepsy Treated With XYWAV | PK: Predose, 0.5 hour, 0.75 hour, 1 hour, 1.5 hour post-first dose and post-second dose, 6 hour post-first dose, 8 hour post-first dose | Blood samples were processed to obtain plasma samples and then analyzed for oxybate concentrations using a validated bioanalytical method. |
| Pharmacokinetic Parameter Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) In a Subset of Participants With Narcolepsy Treated With XYWAV | PK: Predose, 0.5 hour, 0.75 hour, 1 hour, 1.5 hour post-first dose and post-second dose, 6 hour post-first dose, 8 hour post-first dose | Blood samples were processed to obtain plasma samples and then analyzed for oxybate concentrations using a validated bioanalytical method. |
Countries
Canada, United States
Participant flow
Recruitment details
The Enrolled Analysis Set included n=66 Idiopathic Hypersomnia; n=68 Narcolepsy; n=65 \> 9-g Narcolepsy. Each cohort has a cohort-specific ICF and a unique set of protocol specified assessments/procedures. Participants in the \>9-g Narcolepsy cohort were either already taking 9 g/night of Xywav at screening or had titrated to 9 g of Xywav while in the Narcolepsy cohort, discontinued from this cohort, and signed a new ICF to begin the \>9-g Narcolepsy cohort (referred to as "transfer participants").
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous Exploratory >9-g Narcolepsy cohort | 39.2 years STANDARD_DEVIATION 10.92 |
| Age, Continuous IH and Narcolepsy cohorts | 35.6 years STANDARD_DEVIATION 12.5 |
| Race/Ethnicity, Customized Exploratory >9-g Narcolepsy cohort Asian | 1 Participants |
| Race/Ethnicity, Customized Exploratory >9-g Narcolepsy cohort Black or African American | 7 Participants |
| Race/Ethnicity, Customized Exploratory >9-g Narcolepsy cohort Multiple | 1 Participants |
| Race/Ethnicity, Customized Exploratory >9-g Narcolepsy cohort Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Exploratory >9-g Narcolepsy cohort Unknown | 2 Participants |
| Race/Ethnicity, Customized Exploratory >9-g Narcolepsy cohort White | 37 Participants |
| Race/Ethnicity, Customized IH and Narcolepsy cohorts Asian | 2 Participants |
| Race/Ethnicity, Customized IH and Narcolepsy cohorts Black or African American | 3 Participants |
| Race/Ethnicity, Customized IH and Narcolepsy cohorts Multiple | 2 Participants |
| Race/Ethnicity, Customized IH and Narcolepsy cohorts Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized IH and Narcolepsy cohorts Unknown | 1 Participants |
| Race/Ethnicity, Customized IH and Narcolepsy cohorts White | 44 Participants |
| Sex/Gender, Customized Exploratory >9-g Narcolepsy cohort Female (at birth) | 30 Participants |
| Sex/Gender, Customized Exploratory >9-g Narcolepsy cohort Male (at birth) | 18 Participants |
| Sex/Gender, Customized IH and Narcolepsy cohorts Female (at birth) | 37 Participants |
| Sex/Gender, Customized IH and Narcolepsy cohorts Male (at birth) | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 46 | 0 / 55 | 0 / 48 |
| other Total, other adverse events | 34 / 46 | 34 / 55 | 36 / 48 |
| serious Total, serious adverse events | 1 / 46 | 0 / 55 | 1 / 48 |
Outcome results
None listed