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

Jazz Pharmaceuticals

Status and phase: Begins enrollment this month; Phase 3

Conditions: Idiopathic Hypersomnia; Narcolepsy

Treatments: Drug: Xywav; Other: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT07625280

JZP258-304

Details and patient eligibility

About

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).

Full 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.

Enrollment: 108 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Has a primary diagnosis of IH or narcolepsy Type 1 or Type 2 (NT1 or NT2)
2. 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.
3. If currently treated with oxybate, must have documented improvement of EDS with oxybate treatment per the investigator's clinical judgement.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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 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

12. Has recently taken, is taking, or plans to take an Orexin 2 receptor (OX2R) agonist during the study.

13. Has tobacco-use disorder or uses vaping products that impact sleep

14. Has excessive caffeine consumption that may impact sleep

15. Has clinically significant abnormal laboratory values

16. Has an occupation that requires nighttime or variable shift work

17. Has plans for travel across more than 3 time zones during the study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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108 participants in 4 patient groups, including a placebo group

Once-nightly stable dose Xywav group

Active Comparator group

Description:

Participants assigned to cohort 1 will receive once-nightly dosing of Xywav for up to 14 weeks until they reach a stable dose. Once stable dose is achieved, participants will continue taking their stable dose of Xywav for 2 additional weeks.

Treatment:

Drug: Xywav

Once-nightly placebo group

Placebo Comparator group

Description:

Participants assigned to cohort 1 will receive once-nightly dosing of Xywav for up to 14 weeks until they reach a stable dose. Once stable dose is achieved, participants will take placebo for 2 additional weeks.

Treatment:

Other: Placebo

Drug: Xywav

Twice nightly stable dose Xywav group

Active Comparator group

Description:

Participants assigned to cohort 2 will receive twice-nightly dosing of Xywav for up to 14 weeks until they reach a stable dose. Once stable dose is achieved, participants will continue taking their stable dose of Xywav for 2 additional weeks.

Treatment:

Drug: Xywav

Twice nightly placebo group

Placebo Comparator group

Description:

Participants assigned to cohort 2 will receive twice-nightly dosing of Xywav for up to 14 weeks until they reach a stable dose. Once stable dose is achieved, participants will take placebo for 2 additional weeks.

Treatment:

Other: Placebo

Drug: Xywav