Idiopathic Hypersomnia, Narcolepsy
Conditions
Keywords
Xywav, Narcolepsy Type 1, NT1, Narcolepsy Type 2, NT2, IH
Brief summary
The purpose of this study is to evaluate the efficacy and safety of expanded Xywav dosing regimens in adult participants with narcolepsy or idiopathic hypersomnia (IH).
Detailed description
The trial has 3 treatment periods: open label titration and optimization period (OL-TOP), stable dose period (SDP) and the double-blind randomized withdrawal period (DBRWP). Participants will be evaluated by their disease cohort (Narcolepsy and IH). Once eligibility to participate in the trial is confirmed, eligible participants will begin OL-TOP. Participants with narcolepsy and IH will be assigned to receive either a once-nightly expanded dosing of Xywav or a twice-nightly expanded dosing of Xywav. Assignment is dependent on participant's standard oxybate treatment and the treating investigator's decision. During OL-TOP, participants' Xywav dosing will be adjusted until they achieve a stable dose. This period can last up to 12 weeks. Once a stable dose is achieved, participants will begin the SDP. During the SDP, all participants will receive the stable Xywav dose for 2 additional weeks. Afterwards, the participants will begin the DBRWP. During this period, participants will be randomized to either continue on their stable dose of Xywav or receive placebo for 2 more weeks. In total, the participants will receive treatment in the trial for up to 16 weeks.
Interventions
DRUGXywav
0.5 g/ml calcium, magnesium, potassium, and sodium oxybates solution taken by mouth
OTHERPlacebo
Placebo solution taken by mouth
Sponsors
Jazz Pharmaceuticals
Jazz Pharmaceuticals Ireland Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Has a primary diagnosis of IH or narcolepsy Type 1 or Type 2 (NT1 or NT2) 2. Participants with a primary diagnosis of NT1 must have a history of at least 14 cataplexy attacks in a typical 2-week period, based on participant history at the time of diagnosis and prior to initiating treatment. 3. Participants with a primary diagnosis of IH must have an average total nightly sleep time of at least 7 hours, based on participant history at the time of diagnosis and prior to initiating treatment. 4. If not currently treated with oxybate, has clinically significant symptoms of excessive daytime sleepiness (EDS) with an Epworth Sleepiness Scale (ESS) score \> 11 at screening and baseline. 5. If currently treated with oxybate, must have documented improvement of EDS with oxybate treatment per the investigator's clinical judgement. 6. If currently treated with oxybate, has been taking the same stable dosing regimen at a total nightly dosage of 3 g to 9 g (inclusive) for at least 2 months at screening. 7. If previously treated with (and not currently taking) oxybate, must have been off oxybate treatment for at least 2 weeks prior to screening. Must not have previously discontinued oxybate due to reasons related to intolerability, safety, or lack of efficacy. 8. If currently treated with alerting agents, has been taking the same dosage for at least 1 month prior to screening and has no current plans to adjust the dosage during the study period. 9. If currently prescribed non-oxybate anticataplectic medications for cataplexy (NT1 only), must agree to taper off these medications (under the guidance and instruction of the investigator) during the OL-TOP and remain off these medications through the end of the DBRWP. 10. If currently treated with nicotine replacement therapy, has been taking the same dosage for at least 1 month prior to screening and has no current plans to adjust the dosage during the study period. 11. Adequate contraceptive precautions
Exclusion criteria
1. 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. 2. Has succinic semi-aldehyde dehydrogenase deficiency by medical history. 3. Has uncontrolled hypothyroidism as determined by central clinical laboratory test results. 4. Has a current seizure disorder. 5. Has a history of head trauma associated with loss of consciousness in the past 5 years 6. Has a history or presence of bipolar disorder, bipolar-related disorders, schizophrenia, schizophrenia spectrum disorders, or other psychotic disorders 7. Has a history or presence of any unstable or clinically significant medical condition, behavioral or psychiatric disorder, 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. 8. Has any other significant disease or disorder that, in the opinion of the investigator, may either put the participant, other participants, or study staff at risk because of participation in the study, may influence the result of the study, or may affect the participant's safety or ability to take part in the study. 9. Any past or current medical conditions or experience that, in the investigator's clinical judgment, would preclude treatment with a once-nightly dose \> 6 g up to 7.5 g dose or twice-nightly regimen with a total nightly dosage \> 9 g up to 12 g (divided into 2 doses). 10. Has any severe drug allergy or a history of allergic or severe adverse reactions or intolerance to Xyrem, Xywav, Gamma-hydroxybutyrate (GHB), or any components of the dosage forms. 11. Has a history of substance abuse and/or a positive urine drug screen for drugs of abuse or alcohol 12. Has recently taken, is taking, or plans to take any of the following: 1. A substance or medication contraindicated with Xywav use 2. A medication with a known drug-drug interaction with Xywav 3. Medications known to have clinically significant CNS sedating effects 4. Other medications, natural health products, or substances from which the participant experiences clinically significant sedation 13. Has recently taken, is taking, or plans to take an Orexin 2 receptor (OX2R) agonist during the study. 14. Has tobacco-use disorder or uses vaping products that impact sleep 15. Has excessive caffeine consumption that may impact sleep 16. Has clinically significant abnormal laboratory values 17. Has an occupation that requires nighttime or variable shift work 18. Has plans for travel across more than 3 time zones during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Epworth Sleepiness Scale (ESS) scores | End of Stable Dose Period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16) | ESS is a self-administered questionnaire with 8 questions. Each question is scored on a scale ranging from 0 (would never fall asleep) to 3 (high chance of falling asleep). It has a total score ranging from 0 to 24, with a higher score representing increased daytime sleepiness. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in NSS scores in participants with NT1 | End of stable dose period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16) | Narcolepsy Severity Scale (NSS) is a 15-item self-administered questionnaire that assesses the severity and consequences of the 5 major narcolepsy symptoms such as daytime sleepiness, cataplexy, hallucinations, sleep paralysis, and disrupted nighttime sleep. The total score for NSS ranges from 0 to 57, with the higher score indicating greater symptom severity |
| Change in NSS-2 scores in participants with NT2 | End of stable dose period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16) | NSS-2 is a modified NSS self-administered questionnaire with only 12 items (omits questions regarding cataplexy). The total score for NSS-2 ranges from 0 to 44, with the higher score indicating greater symptom severity |
| Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Up to the end of the Safety follow up visit (Up to Week 18) | — |
| Change in average total sleep time | End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 16) | Average total sleep time over a 7-day period as per eDiary recordings |
| Change in average sleep latency | End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 16) | Average time it takes a participant to fall asleep over a 7-day period as per eDiary recordings |
| Change in average wake after sleep onset (WASO) | End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 16) | Average time (in minutes) the participant stays awake after they have fallen asleep over a 7-day period per eDiary recordings |
| Change in average number of awakenings after sleep onset (NAASO) | End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 16) | Average number of nighttime wakings over a 7-day period as per their eDiary recordings |
| Sleep quality | End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 16) | Sleep quality as described by participants across five response categories (Very poor, Poor, Fair, Good, Very good), with higher categories indicating better sleep quality evaluated at end of stable dose period (up to Week 14) and at end of DBRWP (up to Week 16) |
| Sleep episode frequency | End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 16) | Participant-reported frequency of unintentionally falling asleep during the previous day. Response options are: 0 times, 1 time, 2 times, 3 times, and 4 or more times. Higher response categories indicate more frequent unintentional daytime sleep episodes quality evaluated at end of stable dose period (up to Week 14) and at end of DBRWP (up to Week 16). |
| Difficulty maintaining wakefulness | End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 16) | Participant-reported difficulty staying awake during low-stimulation activities. Response options are: Not at all, A little of the time, Some of the time, Most of the time, and All or almost all of the time quality evaluated at end of stable dose period (up to Week 14) and at end of DBRWP (up to Week 16). |
| Percentage of participants reporting minimally, much and very much worse in their CGIc questionnaire for IH or narcolepsy symptoms | At the end of Double-Blind Randomized-Withdrawal Period (up to Week 16) | Clinical Global Impression of Change (CGIc) is a 7-point questionnaire completed by the treating physician that evaluates how the physician thinks the participant is responding to treatment since the end of stable dose period (up to week 14). Responses are graded from 1 (very much improved) to 7 (very much worse) |
| Percentage of participants reporting minimally, much and very much worse in their PGIc questionnaire for IH or narcolepsy symptoms | At the end of Double-Blind Randomized-Withdrawal Period (up to Week 16) | Patient Global Impression of Change (PGIc) is a 7-point questionnaire completed by the participant evaluating how they think they are responding to treatment since the end of stable dose period (up to week 14). Responses are graded from 1 (very much improved) to 7 (very much worse) |
| Change in IHSS scores in participants with IH | End of stable dose period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16) | Idiopathic Hypersomnia Severity Scare (IHSS) is a 14-item self-reported questionnaire that assesses the severity and functional consequences of IH symptoms. Questions capture symptoms of excessive sleepiness, sleep inertia, and long sleep duration. The total score for the IHSS ranges from 0 to 50, with higher scores reflecting greater symptom severity. |
| Change in weekly rate of cataplexy (WRC) in participants with NT1 | End of stable dose period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16) | WRC will be assessed for participants with NT1 using a cataplexy frequency electronic diary. Participants will be recording the number of daily cataplexy attacks experienced. |
| Percentage of participants reporting minimally, much and very much worse in their PGIc questionnaire for sleepiness | At the end of Double-Blind Randomized-Withdrawal Period (up to Week 16) | Patient Global Impression of Change (PGIc) is a 7-point questionnaire completed by the participant evaluating how they think they are responding to treatment since the end of stable dose period (up to week 14). Responses are graded from 1 (very much improved) to 7 (very much worse) |
| Change in Clinical Global Impression of Severity (CGIs) Scores for Narcolepsy/IH symptoms | End of stable dose visit period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16) | CGIs is a 1 item question rated on a 5-point scale completed by the treating physician that evaluates how the physician thinks of the severity of the participant's IH/narcolepsy symptoms since the end of stable dose period (up to week 14). Responses are graded from 1 (normal) to 5 (amongst the most extremely ill patients). |
| Change in Patient Global Impression of Severity (PGIs) Scores for sleepiness | End of stable dose period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16) | PGIs is a 1 item question rated on a 5-point scale completed by the participant that evaluates how the participant thinks of the severity of their sleepiness since the end of stable dose period (up to week 14). Responses are graded from 1 (none/no sleepiness) to 5 (very severe). |
| Change in Patient Global Impression of Severity (PGIs) Scores for Narcolepsy/IH symptoms | End of stable dose visit period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16) | PGIs is a 1 item question rated on a 5-point scale completed by the participant that evaluates how the participant thinks of the severity of their IH/narcolepsy symptoms since the end of stable dose period (up to week 14). Responses are graded from 1 (none/no symptoms) to 5 (very severe). |
Countries
United States
Contacts
CONTACTClinical Trial Disclosure & Transparency
Outcome results
None listed