A Study Evaluating the Efficacy and Safety of Xywav Expanded Dosing vs Placebo in Participants With Narcolepsy or IH

Official title

A Phase 3, Multicenter, Double-blind, Placebo-controlled, Randomized-withdrawal Study to Evaluate the Efficacy and Safety of Expanded Dosing Regimens for Xywav in Adult Participants With Narcolepsy or Idiopathic Hypersomnia

Overview

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 2 treatment periods: titration and optimization period and the randomized withdrawal period. Once eligibility to participate in the trial is confirmed, eligible participants will begin the titration and optimization treatment period where they will be assigned to either cohort 1 or cohort 2. Participants assigned to Cohort 1 will receive once-nightly dosing of Xywav and participants assigned to Cohort 2 will receive twice-nightly dosing of Xywav. Assignment is dependent on participant's standard oxybate treatment and the treating investigator's decision. During the titration and optimization treatment period, participants' Xywav dosing will be adjusted until they achieve a stable dose in this period. This period will last up to 14 weeks. After a stable dose is achieved, the participants will begin the randomized withdrawal treatment period. During the withdrawal treatment period, participants assigned in both cohorts will be randomized to either continue on their stable dose of Xywav or receive placebo for 2 additional weeks of treatment in the trial.

Interventions

• Drug Xywav
  0.5 g/ml calcium, magnesium, potassium, and sodium oxybates solution taken by mouth
• Other Placebo
  Placebo solution taken by mouth

Primary outcome measures

• Change in Epworth Sleepiness Scale (ESS) scores [Time frame: End of stable dose visit (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16)]

Secondary outcome measures (7)

• Clinical Global Impression of Change (CGIc) scores [Time frame: At the end of Double-Blind Randomized-Withdrawal Period (up to Week 16)]
• Patient Global Impression of Change (PGIc) scores [Time frame: At the end of Double-Blind Randomized-Withdrawal Period (up to Week 16)]
• Change in IHSS scores in participants with IH [Time frame: End of stable dose visit (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16)]
• Change in NSS scores in participants with NT1 [Time frame: End of stable dose visit (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16)]
• Change in NSS-2 scores in participants with NT2 [Time frame: End of stable dose visit (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16)]
• Change in weekly rate of cataplexy (WRC) in participants with NT1 [Time frame: End of stable dose visit (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16)]
• Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) [Time frame: Up to the end of the Safety follow up visit (Up to Week 18)]

Eligibility criteria

Inclusion criteria

• Has a primary diagnosis of IH or narcolepsy Type 1 or Type 2 (NT1 or NT2)
• 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.
• If currently treated with oxybate, must have documented improvement of EDS with oxybate treatment per the investigator's clinical judgement.
• 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.
• 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.
• If currently treated with anticataplectics (NT1 only) and/or 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.
• 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.
• Adequate contraceptive precautions

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.
• Has succinic semi-aldehyde dehydrogenase deficiency by medical history.
• Has uncontrolled hypothyroidism as determined by central clinical laboratory test results.
• Has a current seizure disorder.
• Has a history of head trauma associated with loss of consciousness in the past 5 years
• Has a history or presence of bipolar disorder, bipolar-related disorders, schizophrenia, schizophrenia spectrum disorders, or other psychotic disorders
• 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.
• 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.
• 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).
• 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.
• Has recently taken, is taking, or plans to take any of the following:

• A substance or medication contraindicated with Xywav use
• A medication with a known drug-drug interaction with Xywav
• Medications known to have clinically significant CNS sedating effects:
• Other medications, natural health products, or substances from which the participant experiences clinically significant sedation
• Has recently taken, is taking, or plans to take an Orexin 2 receptor (OX2R) agonist during the study.
• Has tobacco-use disorder or uses vaping products that impact sleep
• Has excessive caffeine consumption that may impact sleep
• Has clinically significant abnormal laboratory values
• Has an occupation that requires nighttime or variable shift work
• Has plans for travel across more than 3 time zones during the study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Intrepid Research — Cincinnati

Identifiers

NCT: NCT07625280 · JZP258-304

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗