Trial Outcomes & Findings for An Interventional Safety Switch Study (Segue Study) of XYWAV in Narcolepsy (NCT NCT04794491)

NCT ID: NCT04794491

Last Updated: 2024-01-09

Results Overview

Mean weekly rate of cataplexy attack = (total number of cataplexy attacks reported during the period/number of days during the period where a diary was completed) x 7.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 62 participants
• Primary outcome timeframe: Baseline to Week 8
• Results posted on: 2024-01-09

Participant Flow

A total of 62 participants were enrolled in trial sites across the United States.

Participant milestones

Measure	Overall Participants received JZP258 (XYWAV) at a maximum nightly dosage of 9 g administered orally 1 to 3 times nightly, with no single dose exceeding 6 g.
Overall Study STARTED	62
Overall Study Baseline Period	62
Overall Study Intervention (XYWAV) Period	60
Overall Study Safety Follow-Up Period	59
Overall Study COMPLETED	54
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Measure	Overall Participants received JZP258 (XYWAV) at a maximum nightly dosage of 9 g administered orally 1 to 3 times nightly, with no single dose exceeding 6 g.
Overall Study Adverse Event	1
Overall Study Alcohol or Urine Drug Screen Result Is Positive	4
Overall Study Noncompliance With Study Intervention	1
Overall Study Withdrawal by Subject	2

Baseline Characteristics

An Interventional Safety Switch Study (Segue Study) of XYWAV in Narcolepsy

Baseline characteristics by cohort

Measure	Overall n=62 Participants Participants received JZP258 (XYWAV) at a maximum nightly dosage of 9 g administered orally 1 to 3 times nightly, with no single dose exceeding 6 g.
Age, Continuous	44.3 years STANDARD_DEVIATION 15.22 • n=5 Participants
Sex: Female, Male Female	37 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	58 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants
Race (NIH/OMB) White	54 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Week 8

Population: The weekly rate of cataplexy attacks was assessed using the XYWAV Efficacy Analysis Set, which included all participants in the XYWAV Safety Analysis Set who finished the course of study. Includes Narcolepsy type 1 participants with a mean weekly rate of cataplexy attack at both the first 7 days of the baseline period and the week 8 visit.

Mean weekly rate of cataplexy attack = (total number of cataplexy attacks reported during the period/number of days during the period where a diary was completed) x 7.

Outcome measures

Measure	Overall n=24 Participants Participants received JZP258 (XYWAV) at a maximum nightly dosage of 9 g administered orally 1 to 3 times nightly, with no single dose exceeding 6 g.
Change in Weekly Rate of Cataplexy Attacks	0.98 cataplexy attacks per week Standard Deviation 4.1222

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 8

Population: NVAS was assessed using the XYWAV Efficacy Analysis Set, which included all participants in the XYWAV Safety Analysis Set who finished the course of study. Includes participants with a baseline value and a post-baseline value at the end of treatment (ET) or early discontinuation ( E/D).

Tolerability associated with Xyrem and XYWAV was measured based on an NVAS assessment administered electronically. NVAS was captured daily during the last 7 days of the Baseline (Xyrem-stable dose and regimen) period and the last 7 days of the Intervention period (on XYWAV) prior to the ET visit or prior to the E/D visit, if possible. For participants with at least one day of NVAS data, the NVAS for that week was the average daily score from days with non-missing data within the week, then multiplied by 7. The NVAS ranges 0-100 mm, with higher scores representing more severe/intense nausea.

Outcome measures

Measure	Overall n=47 Participants Participants received JZP258 (XYWAV) at a maximum nightly dosage of 9 g administered orally 1 to 3 times nightly, with no single dose exceeding 6 g.
Change in the Nausea Visual Analog Scale (NVAS)	3.13 score on a scale Standard Deviation 29.089

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 8

Population: PGIC was assessed using the XYWAV Efficacy Analysis Set, which included all participants in the XYWAV Safety Analysis Set who finished the course of study. Includes participants who have at least one PGIc assessment performed at the end of the intervention period or early discontinuation (E/D) visit.

The PGIc is a 7-point Likert-type rating based on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). PGIc values were measured at the ET or E/D, as applicable.

Outcome measures

Measure	Overall n=51 Participants Participants received JZP258 (XYWAV) at a maximum nightly dosage of 9 g administered orally 1 to 3 times nightly, with no single dose exceeding 6 g.
Number of Participants With Patient Global Impression of Change (PGIc) Values Very Much Worse	0 Participants
Number of Participants With Patient Global Impression of Change (PGIc) Values Very Much Improved	1 Participants
Number of Participants With Patient Global Impression of Change (PGIc) Values Much Improved	9 Participants
Number of Participants With Patient Global Impression of Change (PGIc) Values Minimally Improved	12 Participants
Number of Participants With Patient Global Impression of Change (PGIc) Values No Change	26 Participants
Number of Participants With Patient Global Impression of Change (PGIc) Values Minimally Worse	3 Participants
Number of Participants With Patient Global Impression of Change (PGIc) Values Much Worse	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 8

Population: ESS was assessed using the XYWAV Efficacy Analysis Set, which included all participants in the XYWAV Safety Analysis Set who finished the course of study. Includes participants with Epworth Sleeping Scale assessments at both Baseline and ET or E/D visits.

The ESS questionnaire included a set of 8 questions regarding how likely the participant would be to doze off or fall asleep in different situations. The ESS measures EDS or average sleep propensity in daily life. Responses range from 0 = would never doze (better outcome) to 3 = high chance of dozing (worse outcome). Changes in ESS scores were assessed between the Baseline period and ET or E/D, as applicable

Outcome measures

Measure	Overall n=50 Participants Participants received JZP258 (XYWAV) at a maximum nightly dosage of 9 g administered orally 1 to 3 times nightly, with no single dose exceeding 6 g.
Change in Epworth Sleepiness Scale (ESS)	-0.6 units on a scale Standard Deviation 2.33

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 8

Population: The time to achieve an optimized dose and regimen was assessed using the XYWAV Efficacy Analysis Set, which included all participants in the XYWAV Safety Analysis Set who finished the course of study.

Defined as the time from the first dose and regimen to the optimized dose and regimen of XYWAV, where the optimized dose and regimen indicates the final dose and regimen that remains unchanged throughout the remainder of the Intervention period.

Outcome measures

Measure	Overall n=54 Participants Participants received JZP258 (XYWAV) at a maximum nightly dosage of 9 g administered orally 1 to 3 times nightly, with no single dose exceeding 6 g.
Time to Achieve Optimized Dose and Regimen	2.6 day Standard Deviation 4.90

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 8

Population: The number of changes from the first dose and regimen to the optimized was assessed using the XYWAV Efficacy Analysis Set, which included all participants in the XYWAV Safety Analysis Set who finished the course of study.

The amount of times the dose and regimen were changed before an optimized dose and regimen were achieved.

Outcome measures

Measure	Overall n=54 Participants Participants received JZP258 (XYWAV) at a maximum nightly dosage of 9 g administered orally 1 to 3 times nightly, with no single dose exceeding 6 g.
Number of Changes From the First Dose and Regimen to Optimized Dose and Regimen Never Changed	48 Participants
Number of Changes From the First Dose and Regimen to Optimized Dose and Regimen Changed Once	6 Participants
Number of Changes From the First Dose and Regimen to Optimized Dose and Regimen Changed Twice	0 Participants
Number of Changes From the First Dose and Regimen to Optimized Dose and Regimen Changed More than Twice	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 8

Population: The number of participants who dosed fasted versus without food consideration was assessed using the XYWAV Efficacy Analysis Set, which included all participants in the XYWAV Safety Analysis Set who finished the course of study.

Once the participant reached an optimized dose and regimen, the investigator could decide to instruct the participant to dose without regard to food.

Outcome measures

Measure	Overall n=54 Participants Participants received JZP258 (XYWAV) at a maximum nightly dosage of 9 g administered orally 1 to 3 times nightly, with no single dose exceeding 6 g.
Number of Participants Dosing Fasted Versus Dosing Without Consideration of Food Dosing Fasted	53 Participants
Number of Participants Dosing Fasted Versus Dosing Without Consideration of Food Dosing without Food Consideration	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 8

Population: The duration of time between the last meal and dosing was assessed using the XYWAV Efficacy Analysis Set, which included all participants in the XYWAV Safety Analysis Set who finished the course of study.

The difference between the time of day that participants ate their last meal and the time of day participants take their first dose.

Outcome measures

Measure	Overall n=54 Participants Participants received JZP258 (XYWAV) at a maximum nightly dosage of 9 g administered orally 1 to 3 times nightly, with no single dose exceeding 6 g.
Duration of Time Between the Last Meal Relative to Dosing	113.7 minute Standard Deviation 313.31

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 8

Population: Characterization of meals was assessed using the XYWAV Efficacy Analysis Set, which included all participants in the XYWAV Safety Analysis Set who finished the course of study.

Types of meals consumed before dosing.

Outcome measures

Measure	Overall n=54 Participants Participants received JZP258 (XYWAV) at a maximum nightly dosage of 9 g administered orally 1 to 3 times nightly, with no single dose exceeding 6 g.
Characterization of Meals Relative to Dosing Regular Meal	54 Participants
Characterization of Meals Relative to Dosing Snack	45 Participants
Characterization of Meals Relative to Dosing Beverage Other than Water	19 Participants

Adverse Events

Overall

Serious events: 2 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Measure	Overall n=60 participants at risk Overall XYWAV safety analysis set.
Metabolism and nutrition disorders Hyperkalaemia	1.7% 1/60 • Treatment-emergent adverse event (TEAE) data were collected from up to 30 days before Day 1 up to week 10 + 3 days. A TEAE is defined as an AE that either began or worsened after administration of the first dose of study intervention (XYWAV) to End of Treatment Period (prior to the Safety Follow-up Period). Adverse events were assessed using the XYWAV Safety Analysis set, which included all participants in the Safety Analysis Set who received at least 1 dose of XYWAV.
Injury, poisoning and procedural complications Fall	1.7% 1/60 • Treatment-emergent adverse event (TEAE) data were collected from up to 30 days before Day 1 up to week 10 + 3 days. A TEAE is defined as an AE that either began or worsened after administration of the first dose of study intervention (XYWAV) to End of Treatment Period (prior to the Safety Follow-up Period). Adverse events were assessed using the XYWAV Safety Analysis set, which included all participants in the Safety Analysis Set who received at least 1 dose of XYWAV.

Other adverse events

Measure	Overall n=60 participants at risk Overall XYWAV safety analysis set.
Gastrointestinal disorders Diarrhoea	3.3% 2/60 • Treatment-emergent adverse event (TEAE) data were collected from up to 30 days before Day 1 up to week 10 + 3 days. A TEAE is defined as an AE that either began or worsened after administration of the first dose of study intervention (XYWAV) to End of Treatment Period (prior to the Safety Follow-up Period). Adverse events were assessed using the XYWAV Safety Analysis set, which included all participants in the Safety Analysis Set who received at least 1 dose of XYWAV.
Gastrointestinal disorders Nausea	3.3% 2/60 • Treatment-emergent adverse event (TEAE) data were collected from up to 30 days before Day 1 up to week 10 + 3 days. A TEAE is defined as an AE that either began or worsened after administration of the first dose of study intervention (XYWAV) to End of Treatment Period (prior to the Safety Follow-up Period). Adverse events were assessed using the XYWAV Safety Analysis set, which included all participants in the Safety Analysis Set who received at least 1 dose of XYWAV.
Gastrointestinal disorders Haemorrhoids	1.7% 1/60 • Treatment-emergent adverse event (TEAE) data were collected from up to 30 days before Day 1 up to week 10 + 3 days. A TEAE is defined as an AE that either began or worsened after administration of the first dose of study intervention (XYWAV) to End of Treatment Period (prior to the Safety Follow-up Period). Adverse events were assessed using the XYWAV Safety Analysis set, which included all participants in the Safety Analysis Set who received at least 1 dose of XYWAV.
General disorders Chills	1.7% 1/60 • Treatment-emergent adverse event (TEAE) data were collected from up to 30 days before Day 1 up to week 10 + 3 days. A TEAE is defined as an AE that either began or worsened after administration of the first dose of study intervention (XYWAV) to End of Treatment Period (prior to the Safety Follow-up Period). Adverse events were assessed using the XYWAV Safety Analysis set, which included all participants in the Safety Analysis Set who received at least 1 dose of XYWAV.
General disorders Oedema peripheral	1.7% 1/60 • Treatment-emergent adverse event (TEAE) data were collected from up to 30 days before Day 1 up to week 10 + 3 days. A TEAE is defined as an AE that either began or worsened after administration of the first dose of study intervention (XYWAV) to End of Treatment Period (prior to the Safety Follow-up Period). Adverse events were assessed using the XYWAV Safety Analysis set, which included all participants in the Safety Analysis Set who received at least 1 dose of XYWAV.
Infections and infestations COVID-19	3.3% 2/60 • Treatment-emergent adverse event (TEAE) data were collected from up to 30 days before Day 1 up to week 10 + 3 days. A TEAE is defined as an AE that either began or worsened after administration of the first dose of study intervention (XYWAV) to End of Treatment Period (prior to the Safety Follow-up Period). Adverse events were assessed using the XYWAV Safety Analysis set, which included all participants in the Safety Analysis Set who received at least 1 dose of XYWAV.
Infections and infestations Nasopharyngitis	3.3% 2/60 • Treatment-emergent adverse event (TEAE) data were collected from up to 30 days before Day 1 up to week 10 + 3 days. A TEAE is defined as an AE that either began or worsened after administration of the first dose of study intervention (XYWAV) to End of Treatment Period (prior to the Safety Follow-up Period). Adverse events were assessed using the XYWAV Safety Analysis set, which included all participants in the Safety Analysis Set who received at least 1 dose of XYWAV.
Infections and infestations Conjunctivitis	1.7% 1/60 • Treatment-emergent adverse event (TEAE) data were collected from up to 30 days before Day 1 up to week 10 + 3 days. A TEAE is defined as an AE that either began or worsened after administration of the first dose of study intervention (XYWAV) to End of Treatment Period (prior to the Safety Follow-up Period). Adverse events were assessed using the XYWAV Safety Analysis set, which included all participants in the Safety Analysis Set who received at least 1 dose of XYWAV.
Infections and infestations Sinusitis	1.7% 1/60 • Treatment-emergent adverse event (TEAE) data were collected from up to 30 days before Day 1 up to week 10 + 3 days. A TEAE is defined as an AE that either began or worsened after administration of the first dose of study intervention (XYWAV) to End of Treatment Period (prior to the Safety Follow-up Period). Adverse events were assessed using the XYWAV Safety Analysis set, which included all participants in the Safety Analysis Set who received at least 1 dose of XYWAV.
Injury, poisoning and procedural complications Arthropod bite	1.7% 1/60 • Treatment-emergent adverse event (TEAE) data were collected from up to 30 days before Day 1 up to week 10 + 3 days. A TEAE is defined as an AE that either began or worsened after administration of the first dose of study intervention (XYWAV) to End of Treatment Period (prior to the Safety Follow-up Period). Adverse events were assessed using the XYWAV Safety Analysis set, which included all participants in the Safety Analysis Set who received at least 1 dose of XYWAV.
Injury, poisoning and procedural complications Intentional overdose	1.7% 1/60 • Treatment-emergent adverse event (TEAE) data were collected from up to 30 days before Day 1 up to week 10 + 3 days. A TEAE is defined as an AE that either began or worsened after administration of the first dose of study intervention (XYWAV) to End of Treatment Period (prior to the Safety Follow-up Period). Adverse events were assessed using the XYWAV Safety Analysis set, which included all participants in the Safety Analysis Set who received at least 1 dose of XYWAV.
Injury, poisoning and procedural complications Sedation complication	1.7% 1/60 • Treatment-emergent adverse event (TEAE) data were collected from up to 30 days before Day 1 up to week 10 + 3 days. A TEAE is defined as an AE that either began or worsened after administration of the first dose of study intervention (XYWAV) to End of Treatment Period (prior to the Safety Follow-up Period). Adverse events were assessed using the XYWAV Safety Analysis set, which included all participants in the Safety Analysis Set who received at least 1 dose of XYWAV.
Investigations Urobilinogen urine increased	1.7% 1/60 • Treatment-emergent adverse event (TEAE) data were collected from up to 30 days before Day 1 up to week 10 + 3 days. A TEAE is defined as an AE that either began or worsened after administration of the first dose of study intervention (XYWAV) to End of Treatment Period (prior to the Safety Follow-up Period). Adverse events were assessed using the XYWAV Safety Analysis set, which included all participants in the Safety Analysis Set who received at least 1 dose of XYWAV.
Metabolism and nutrition disorders Hyperkalaemia	1.7% 1/60 • Treatment-emergent adverse event (TEAE) data were collected from up to 30 days before Day 1 up to week 10 + 3 days. A TEAE is defined as an AE that either began or worsened after administration of the first dose of study intervention (XYWAV) to End of Treatment Period (prior to the Safety Follow-up Period). Adverse events were assessed using the XYWAV Safety Analysis set, which included all participants in the Safety Analysis Set who received at least 1 dose of XYWAV.
Musculoskeletal and connective tissue disorders Exostosis	1.7% 1/60 • Treatment-emergent adverse event (TEAE) data were collected from up to 30 days before Day 1 up to week 10 + 3 days. A TEAE is defined as an AE that either began or worsened after administration of the first dose of study intervention (XYWAV) to End of Treatment Period (prior to the Safety Follow-up Period). Adverse events were assessed using the XYWAV Safety Analysis set, which included all participants in the Safety Analysis Set who received at least 1 dose of XYWAV.
Nervous system disorders Headache	3.3% 2/60 • Treatment-emergent adverse event (TEAE) data were collected from up to 30 days before Day 1 up to week 10 + 3 days. A TEAE is defined as an AE that either began or worsened after administration of the first dose of study intervention (XYWAV) to End of Treatment Period (prior to the Safety Follow-up Period). Adverse events were assessed using the XYWAV Safety Analysis set, which included all participants in the Safety Analysis Set who received at least 1 dose of XYWAV.
Nervous system disorders Migraine	1.7% 1/60 • Treatment-emergent adverse event (TEAE) data were collected from up to 30 days before Day 1 up to week 10 + 3 days. A TEAE is defined as an AE that either began or worsened after administration of the first dose of study intervention (XYWAV) to End of Treatment Period (prior to the Safety Follow-up Period). Adverse events were assessed using the XYWAV Safety Analysis set, which included all participants in the Safety Analysis Set who received at least 1 dose of XYWAV.
Nervous system disorders Paraesthesia	1.7% 1/60 • Treatment-emergent adverse event (TEAE) data were collected from up to 30 days before Day 1 up to week 10 + 3 days. A TEAE is defined as an AE that either began or worsened after administration of the first dose of study intervention (XYWAV) to End of Treatment Period (prior to the Safety Follow-up Period). Adverse events were assessed using the XYWAV Safety Analysis set, which included all participants in the Safety Analysis Set who received at least 1 dose of XYWAV.
Nervous system disorders Somnolence	1.7% 1/60 • Treatment-emergent adverse event (TEAE) data were collected from up to 30 days before Day 1 up to week 10 + 3 days. A TEAE is defined as an AE that either began or worsened after administration of the first dose of study intervention (XYWAV) to End of Treatment Period (prior to the Safety Follow-up Period). Adverse events were assessed using the XYWAV Safety Analysis set, which included all participants in the Safety Analysis Set who received at least 1 dose of XYWAV.
Psychiatric disorders Initial insomnia	1.7% 1/60 • Treatment-emergent adverse event (TEAE) data were collected from up to 30 days before Day 1 up to week 10 + 3 days. A TEAE is defined as an AE that either began or worsened after administration of the first dose of study intervention (XYWAV) to End of Treatment Period (prior to the Safety Follow-up Period). Adverse events were assessed using the XYWAV Safety Analysis set, which included all participants in the Safety Analysis Set who received at least 1 dose of XYWAV.
Psychiatric disorders Suicidal ideation	1.7% 1/60 • Treatment-emergent adverse event (TEAE) data were collected from up to 30 days before Day 1 up to week 10 + 3 days. A TEAE is defined as an AE that either began or worsened after administration of the first dose of study intervention (XYWAV) to End of Treatment Period (prior to the Safety Follow-up Period). Adverse events were assessed using the XYWAV Safety Analysis set, which included all participants in the Safety Analysis Set who received at least 1 dose of XYWAV.
Renal and urinary disorders Urine abnormality	1.7% 1/60 • Treatment-emergent adverse event (TEAE) data were collected from up to 30 days before Day 1 up to week 10 + 3 days. A TEAE is defined as an AE that either began or worsened after administration of the first dose of study intervention (XYWAV) to End of Treatment Period (prior to the Safety Follow-up Period). Adverse events were assessed using the XYWAV Safety Analysis set, which included all participants in the Safety Analysis Set who received at least 1 dose of XYWAV.
Skin and subcutaneous tissue disorders Night sweats	3.3% 2/60 • Treatment-emergent adverse event (TEAE) data were collected from up to 30 days before Day 1 up to week 10 + 3 days. A TEAE is defined as an AE that either began or worsened after administration of the first dose of study intervention (XYWAV) to End of Treatment Period (prior to the Safety Follow-up Period). Adverse events were assessed using the XYWAV Safety Analysis set, which included all participants in the Safety Analysis Set who received at least 1 dose of XYWAV.
Skin and subcutaneous tissue disorders Rash	1.7% 1/60 • Treatment-emergent adverse event (TEAE) data were collected from up to 30 days before Day 1 up to week 10 + 3 days. A TEAE is defined as an AE that either began or worsened after administration of the first dose of study intervention (XYWAV) to End of Treatment Period (prior to the Safety Follow-up Period). Adverse events were assessed using the XYWAV Safety Analysis set, which included all participants in the Safety Analysis Set who received at least 1 dose of XYWAV.
Vascular disorders Hot flush	1.7% 1/60 • Treatment-emergent adverse event (TEAE) data were collected from up to 30 days before Day 1 up to week 10 + 3 days. A TEAE is defined as an AE that either began or worsened after administration of the first dose of study intervention (XYWAV) to End of Treatment Period (prior to the Safety Follow-up Period). Adverse events were assessed using the XYWAV Safety Analysis set, which included all participants in the Safety Analysis Set who received at least 1 dose of XYWAV.

Additional Information

Clinical Trial Disclosure & Transparency

Jazz Pharmaceuticals

Phone: 215-832-3750

Email: ClinicalTrialDisclosure@jazzpharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place