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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-000426-20 | EudraCT Number |
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This is a double-blind, placebo-controlled, randomized-withdrawal, multicenter study of the efficacy and safety of JZP-258.
Subjects will be transitioned to JZP-258 based on their treatment status at study entry. All subjects will begin JZP-258 treatment at the beginning of this period and continue through Week 12. They will be treated with JZP-258 alone for the final two weeks of this 12-week period. Once the JZP-258 dose has been optimized per the Investigator's judgment, these subjects may enter the 2-week Stable-Dose Period with that dose. Subjects are eligible to enter the Double-Blind Randomized-Withdrawal Period if the dose of JZP-258 remains unchanged during the Stable-Dose Period and, in the judgment of the Investigator, no clinically significant worsening in narcolepsy symptoms or clinically significant adverse events due to JZP-258 treatment have occurred. Subjects will return for a Safety Follow-up visit 2 weeks after the Double-Blind Randomized-Withdrawal Period. Subjects who complete the double-blind treatment period during the Main Study are eligible to enter a 24-week Open-Label Extension. During this period subjects will receive open label JZP-258. Subjects will return for a Safety Follow-up visit 2 weeks after the Open-Label Extension Period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Placebo |
|
| JZP-258 | Experimental | JZP-258 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| JZP-258 | Drug | JZP-258 oral solution 0.5 g/mL, which is equivalent to 0.413 g/mL of oxybate |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Weekly Number of Cataplexy Attacks | Participants completed a daily Cataplexy Frequency Diary each night prior to bedtime. Participants were to record the number of cataplexy attacks that they had each day. | Change from baseline (2 weeks of the Stable Dose Period) to the 2 weeks of the Double Blind Randomized Withdrawal Period (DB RWP) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in the Epworth Sleepiness Scale (ESS) Score | This is the key secondary endpoint. The Epworth Sleepiness Scale (ESS) was a self-administered questionnaire with 8 questions. Participants were asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. Most participants engaged in those activities at least occasionally, although not necessarily every day. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that participants average sleep propensity in daily life (ASP), or their 'daytime sleepiness'. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Director Clinical Trial Disclosure & Transparency | Jazz Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| SDS Clinical Trials, Inc. | Orange | California | 92858 | United States | ||
| Stanford Health Services |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36947322 | Derived | Bogan RK, Foldvary-Schaefer N, Skowronski R, Chen A, Thorpy MJ. Long-Term Safety and Tolerability During a Clinical Trial and Open-Label Extension of Low-Sodium Oxybate in Participants with Narcolepsy with Cataplexy. CNS Drugs. 2023 Apr;37(4):323-335. doi: 10.1007/s40263-023-00992-y. Epub 2023 Mar 22. | |
| 35635687 | Derived |
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Subjects were evaluated for eligibility during the Screening Period (up to 30 days).
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| ID | Title | Description |
|---|---|---|
| FG000 | Open-label JZP-258 | All 201 subjects entered the Open Label Optimized Treatment and Titration Period (OL OTTP) and received at least 1 dose of study drug. During the OL OTTP (12 weeks), eligible subjects were transitioned to JZP-258 treatment based on their pre-treatment status. During the Stable Dose Period, subjects received open-label JZP-258 at the same unchanged dose that they received during the last 2 weeks of the Open Label Treatment and Titration Period. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Open Label Treatment and Titration |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 15, 2018 | Aug 19, 2020 |
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| Placebo | Other | Matching placebo solution (aqueous solution containing sodium citrate, malic acid, and sucralose; all ingredients were compendial [United States Pharmacopeia/ National Formulary]) |
|
| From the end of the Stable Dose Period to the end of the Double Blind Randomized Withdrawal Period |
| Number of Participants With Worsening Patient Global Impression of Change (PGIc) for Narcolepsy Overall | At the end of the Double Blind Randomized Withdrawal Period (DB RWP), participants rated the change in their condition on a 7-point scale ranging from 1 = "very much improved" to 7 = "very much worse" since the last visit. This endpoint measures the percentage of participants with worsening PGIc scores for narcolepsy overall (defined as scores of Much Worse or Very Much Worse). | At the end of the Double Blind Randomized Withdrawal Period |
| Number of Participants With Worsening Clinical Global Impression of Change (CGIc) for Narcolepsy Overall | At the end of the Double Blind Randomized Withdrawal Period, Investigators rated their impression of any change in the severity of the participant's narcolepsy overall condition since the start of the Double Blind Randomized Withdrawal Period on a 7-point scale ranging from 1 = "very much improved" to 7 = "very much worse". This endpoint measures the percentage of participants with worsening CGIc scores for narcolepsy overall, defined as scores of Much Worse or Very Much Worse. | At the end of the Double Blind Randomized Withdrawal Period |
| Change in 36-Item Short Form Health Survey Version 2 (SF-36v2) Scores | The SF-36v2 is a multi-purpose, short-form health survey with 36 questions/ items. It yields an 8-scale profile of functional health and well-being scores as well as a psychometrically-based physical and mental overall component summary measures. Two summary scores were derived using the SF-36v2. Physical Component Summary measures dimensions of functional health that are meaningful to respondents, including the impact of health and health-related changes on physical function, pain, and the ability to carry out daily roles. The Mental Component Summary component scale measures the impact of health and health-related changes on well-being, including vitality, social function, and emotional well-being. Participants self-report on items in a summary that have between 2-6 choices per item (e.g. none of the time, some of the time, etc.). Summations of item scores were transformed into a range from 0 to 100; zero= worst HRQL, 100=best HRQL. Higher scores indicate better health status. | At the End of the Stable Dose Period to the End of the Double Blind Randomized Withdrawal Period |
| Change in 5-level EQ-5D (EQ-5D-5L) Crosswalk Index Score and Visual Analog Scale | The EQ-5D-5L is a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/ discomfort, and anxiety/ depression). The EQ-5D-5L includes 5 levels of severity for each of the 5 dimensions of the descriptive system (1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems) that reflect increasing levels of difficulty. The 5 digit health states for each dimension are converted into a single value per country (0= equivalent to death, 1= equivalent to best imaginable health and values below 0= health states rated worse than death capped at -1), using the EQ-5D-5L crosswalk index value calculator as recommended by EuroQol group. A visual analogue scale (VAS) used within this scale recorded the participants self-rated health on a VAS and the endpoints resulted in a numeric value set ranging from 0 (= worst imaginable health state) up to 100 (= best imaginable health state). | At the End of the Stable Dose Period to the End of the Double Blind Randomized Withdrawal Period |
| Stanford |
| California |
| 94305 |
| United States |
| Colorado Sleep Institute | Boulder | Colorado | 80301 | United States |
| Pulmonary Disease Specialists | Kissimmee | Florida | 34741 | United States |
| Fort Wayne Neurological Center | Fort Wayne | Indiana | 46804 | United States |
| Kentucky Research Group | Louisville | Kentucky | 40218 | United States |
| Center for Sleep & Wake Disorders | Chevy Chase | Maryland | 20815 | United States |
| Montefiore/ Sleep-Wake Disorders Center | The Bronx | New York | 10467 | United States |
| Gastonia Medical Specialty Clinic | Gastonia | North Carolina | 94305 | United States |
| Research Carolina | Huntersville | North Carolina | 28078 | United States |
| Intrepid Research | Cincinnati | Ohio | 45245 | United States |
| Cleveland Clinic, Sleep Disorder Center | Cleveland | Ohio | 44195 | United States |
| UZ Antwerpen | Edegem | 2650 | Belgium |
| Universitair Ziekenhuis Gent | Ghent | 9000 | Belgium |
| UZ Leuven | Leuven | 3000 | Belgium |
| Fakultni nemocnice Ostrava | Ostrava-Poruba | 70800 | Czechia |
| Vseobecna fakultni nemocnice v Praze | Prague | 128 21 | Czechia |
| Helsingin Uniklinikka, Vitalmed Oy | Helsinki | 00380 | Finland |
| Hôpital Gui de Chauliac | Montpellier | Herault | 34295 | France |
| Hopital Roger Salengro - CHU Lille | Lille | 59037 | France |
| Hospital Universitari Vall d'Hebron | Barcelona | 08035 | Spain |
| Hospital Clinic i Provincial de Barcelona | Barcelona | 08036 | Spain |
| Hospital General de Castellón | Castelló | 12004 | Spain |
| Instituto de Investigaciones del Sueño | Madrid | 28036 | Spain |
| Hospital Vithas Nuestra Señora de America | Madrid | 28043 | Spain |
| Dauvilliers Y, Sonka K, Bogan RK, Partinen M, Del Rio Villegas R, Foldvary-Schaefer N, Skowronski R, Chen A, Black J, Skobieranda F, Thorpy MJ. Changes in Cataplexy Frequency in a Clinical Trial of Lower-Sodium Oxybate with Taper and Discontinuation of Other Anticataplectic Medications. CNS Drugs. 2022 Jun;36(6):633-647. doi: 10.1007/s40263-022-00926-0. Epub 2022 May 30. |
| 33184650 | Derived | Bogan RK, Thorpy MJ, Dauvilliers Y, Partinen M, Del Rio Villegas R, Foldvary-Schaefer N, Skowronski R, Tang L, Skobieranda F, Sonka K. Efficacy and safety of calcium, magnesium, potassium, and sodium oxybates (lower-sodium oxybate [LXB]; JZP-258) in a placebo-controlled, double-blind, randomized withdrawal study in adults with narcolepsy with cataplexy. Sleep. 2021 Mar 12;44(3):zsaa206. doi: 10.1093/sleep/zsaa206. |
| FG001 | JZP-258 | JZP-258 at the dose taken during the last 2 weeks of the Stable Dose Period. |
| FG002 | Placebo | A matching oral solution to JZP-258. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Stable Dose |
|
|
| Double Blind Randomized Withdrawal |
|
|
| Open-label Extension |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Open Label Treatment and Titration | All 201 subjects entered the Open Label Optimized Treatment and Titration Period (OL OTTP) and received at least 1 dose of study drug. During the OL OTTP (12 weeks), eligible subjects were transitioned to JZP-258 treatment based on their pre-treatment status. During the Stable Dose Period, subjects received open-label JZP-258 at the same unchanged dose that they received during the last 2 weeks of the Open Label Treatment and Titration Period. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Weekly Number of Cataplexy Attacks | Participants completed a daily Cataplexy Frequency Diary each night prior to bedtime. Participants were to record the number of cataplexy attacks that they had each day. | The efficacy population contains all randomized subjects who received at least one dose of double-blind study drug and had at least one set of post-randomization efficacy data. | Posted | Median | Inter-Quartile Range | attacks | Change from baseline (2 weeks of the Stable Dose Period) to the 2 weeks of the Double Blind Randomized Withdrawal Period (DB RWP) |
|
|
| ||||||||||||||||||||||||||||
| Secondary | Change in the Epworth Sleepiness Scale (ESS) Score | This is the key secondary endpoint. The Epworth Sleepiness Scale (ESS) was a self-administered questionnaire with 8 questions. Participants were asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. Most participants engaged in those activities at least occasionally, although not necessarily every day. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that participants average sleep propensity in daily life (ASP), or their 'daytime sleepiness'. | The efficacy population contains all randomized subjects who received at least one dose of double-blind study drug and had at least one set of post-randomization efficacy data. | Posted | Median | Inter-Quartile Range | score on a scale | From the end of the Stable Dose Period to the end of the Double Blind Randomized Withdrawal Period |
|
| |||||||||||||||||||||||||||||
| Secondary | Number of Participants With Worsening Patient Global Impression of Change (PGIc) for Narcolepsy Overall | At the end of the Double Blind Randomized Withdrawal Period (DB RWP), participants rated the change in their condition on a 7-point scale ranging from 1 = "very much improved" to 7 = "very much worse" since the last visit. This endpoint measures the percentage of participants with worsening PGIc scores for narcolepsy overall (defined as scores of Much Worse or Very Much Worse). | The efficacy population contains all randomized subjects who received at least one dose of double-blind study drug and had at least one set of post-randomization efficacy data. | Posted | Count of Participants | Participants | At the end of the Double Blind Randomized Withdrawal Period |
|
| ||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Worsening Clinical Global Impression of Change (CGIc) for Narcolepsy Overall | At the end of the Double Blind Randomized Withdrawal Period, Investigators rated their impression of any change in the severity of the participant's narcolepsy overall condition since the start of the Double Blind Randomized Withdrawal Period on a 7-point scale ranging from 1 = "very much improved" to 7 = "very much worse". This endpoint measures the percentage of participants with worsening CGIc scores for narcolepsy overall, defined as scores of Much Worse or Very Much Worse. | The efficacy population contains all randomized subjects who received at least one dose of double-blind study drug and had at least one set of post-randomization efficacy data. | Posted | Count of Participants | Participants | At the end of the Double Blind Randomized Withdrawal Period |
|
| ||||||||||||||||||||||||||||||
| Secondary | Change in 36-Item Short Form Health Survey Version 2 (SF-36v2) Scores | The SF-36v2 is a multi-purpose, short-form health survey with 36 questions/ items. It yields an 8-scale profile of functional health and well-being scores as well as a psychometrically-based physical and mental overall component summary measures. Two summary scores were derived using the SF-36v2. Physical Component Summary measures dimensions of functional health that are meaningful to respondents, including the impact of health and health-related changes on physical function, pain, and the ability to carry out daily roles. The Mental Component Summary component scale measures the impact of health and health-related changes on well-being, including vitality, social function, and emotional well-being. Participants self-report on items in a summary that have between 2-6 choices per item (e.g. none of the time, some of the time, etc.). Summations of item scores were transformed into a range from 0 to 100; zero= worst HRQL, 100=best HRQL. Higher scores indicate better health status. | The efficacy population contains all randomized subjects who received at least one dose of double-blind study drug and had at least one set of post-randomization efficacy data. | Posted | Median | Inter-Quartile Range | score on a scale | At the End of the Stable Dose Period to the End of the Double Blind Randomized Withdrawal Period |
| ||||||||||||||||||||||||||||||
| Secondary | Change in 5-level EQ-5D (EQ-5D-5L) Crosswalk Index Score and Visual Analog Scale | The EQ-5D-5L is a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/ discomfort, and anxiety/ depression). The EQ-5D-5L includes 5 levels of severity for each of the 5 dimensions of the descriptive system (1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems) that reflect increasing levels of difficulty. The 5 digit health states for each dimension are converted into a single value per country (0= equivalent to death, 1= equivalent to best imaginable health and values below 0= health states rated worse than death capped at -1), using the EQ-5D-5L crosswalk index value calculator as recommended by EuroQol group. A visual analogue scale (VAS) used within this scale recorded the participants self-rated health on a VAS and the endpoints resulted in a numeric value set ranging from 0 (= worst imaginable health state) up to 100 (= best imaginable health state). | There were 68 JZP-258 participants included in the Crosswalk Index, and 69 JZP-258 participants in the VAS Score. The efficacy population contains all randomized subjects who received at least one dose of double-blind study drug and had at least one set of post-randomization efficacy data. | Posted | Median | Inter-Quartile Range | score on a scale | At the End of the Stable Dose Period to the End of the Double Blind Randomized Withdrawal Period |
|
Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | JZP-258 | JZP-258 at the dose taken during the last 2 weeks of the Stable Dose Period. | 0 | 201 | 5 | 201 | 108 | 201 |
| EG001 | Placebo | A matching oral solution to JZP-258. | 0 | 65 | 2 | 65 | 12 | 65 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Accidental overdose | Injury, poisoning and procedural complications | MedDRA (19.1) | Systematic Assessment |
| |
| Muscle enzyme increased | Investigations | MedDRA (19.1) | Systematic Assessment |
| |
| Invasive ductal breast carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (19.1) | Systematic Assessment |
| |
| Peripheral nerve paresis | Nervous system disorders | MedDRA (19.1) | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA (19.1) | Systematic Assessment |
| |
| Bile duct stone | Hepatobiliary disorders | MedDRA (19.1) | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA (19.1) | Systematic Assessment |
| |
| Viral cardiomyopathy | Infections and infestations | MedDRA (19.1) | Systematic Assessment |
| |
| Hallucination | Psychiatric disorders | MedDRA (19.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cataplexy | Nervous system disorders | MedDRA (19.1) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (19.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (19.1) | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA (19.1) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (19.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (19.1) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (19.1) | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA (19.1) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (19.1) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (19.1) | Systematic Assessment |
|
The sponsor can review trial results communications prior to public release and can embargo such communications for a period of at least 60 days from the time submitted to sponsor for review. If requested by sponsor, the PI will withhold publication for up to an additional 30 days. Furthermore, the first publication of study results must be a joint publication of all study sites unless a joint manuscript has not been submitted for publication within 12 months of completion of the study.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director, Clinical Trial Disclosure & Transparency | Jazz Pharmaceuticals | 2158709177 | ClinicalTrialDisclosure@JazzPharma.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 25, 2019 | Nov 10, 2020 | SAP_003.pdf |
Not provided
| ID | Term |
|---|---|
| D009290 | Narcolepsy |
| ID | Term |
|---|---|
| D006970 | Disorders of Excessive Somnolence |
| D020919 | Sleep Disorders, Intrinsic |
| D020920 | Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
| D001523 | Mental Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| D012978 | Sodium Oxybate |
| ID | Term |
|---|---|
| D006885 | Hydroxybutyrates |
| D002087 | Butyrates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D006880 | Hydroxy Acids |
Not provided
Not provided
| Lost to Follow-up |
|
| Randomized in error |
|
| Withdrawal by Subject |
|
| Lack of Efficacy |
|
| Other Reason |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Participants |
|
|
|
|
|
A matching oral solution to JZP-258. |
|
|
| OG001 |
| Placebo |
A matching oral solution to JZP-258. |
|
|