Treatment of cataplexy in narcolepsy Treatment of excessive daytime sleepiness (EDS) in narcolepsy MedDRA version: 20.1 Level: LLT Classification code 10015595 Term: Excessive daytime sleepiness System Organ Class: 100000004852 MedDRA version: 20.0 Level: LLT Classification code 10007738 Term: Cataplexy and narcolepsy Sy
Conditions
Interventions
Product Name: JZP-258, 500mg/ml oral solution
Product Code: JZP-258
Pharmaceutical Form: Oral solution
INN or Proposed INN: oxybate (4-hydroxybutanoic a
Sponsors
Jazz Pharmaceuticals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Main Study 1. Male or female subjects between 18 and 70 years of age, inclusive at screening. 2. Have a primary diagnosis of narcolepsy with cataplexy that meets ICSD-3 criteria or DSM-5 criteria, and currently untreated or treated with or without anticataplectics. 3. Have a history of having at least 14 cataplexy attacks in a typical 2-week period and clinically significant symptoms of EDS prior to any narcolepsy treatment. 4. Treatment status (Pre-randomization Group) at study entry: a) Have been taking Xyrem at unchanged doses (twice or thrice nightly dosing no higher than a total of 9 g/night), for the treatment of cataplexy in narcolepsy for at least 2 months prior to screening; or b) Have been taking Xyrem at unchanged doses (twice or thrice nightly dosing no higher than a total of 9 g/night), and another anticataplectic (TCA, SNRI, SSRI, atomoxetine, or other) for the treatment of cataplexy in narcolepsy for at least 2 months prior to screening; or c) Treated with a non-Xyrem anticataplectic (TCA, SNRI, SSRI, atomoxetine, or other) and not treated with Xyrem; or d) Not treated with any agent with anticataplectic properties. 5. If currently treated with Xyrem, must have documented clinical improvement of cataplexy and EDS per Investigator's clinical judgment. 6. If applicable, treated with a stimulant or alerting agent at unchanged doses for at least 2 months prior to dosing or not treated with a stimulant or alerting agent. 7. Have used a medically acceptable method of contraception* for at least 2 months prior to the first dose of study drug and consent to use a medically acceptable method of contraception throughout the entire study period and for 90 days after the study is completed. 8. Willing and able to comply with the study design schedule and other requirements. 9. Willing and able to provide written informed consent. Open Label 1.Completion of the JZP-258 double-blind treatment and completion of Visit 16 2.Is able, in the opinion of the investigator, to take JZP-258 for an additional 24 weeks 3.Agrees to continue to use a medically acceptable method of contraception throughout the entire study period and for 90 days after the Open-Label Extension is completed. 4.Willing and able to comply with the study design schedule and other requirements. 5.Willing and able to provide written informed consent for Open-Label Extension. 6.If currently being treated with Xyrem, the subject's total twice nightly Xyrem dose must be no higher than 9 g/night Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 167 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 18
Exclusion criteria
Exclusion criteria: Main study 1. Narcolepsy secondary to another medical condition(e.g., CNS injury or lesion). 2. Restless leg syndrome (RLS) requiring treatment other than iron supplements. 3. Succinic semi-aldehyde dehydrogenase deficiency (SSADH). 4. Uncontrolled hypothyroidism. 5. History of seizures, excluding early childhood non-pathological febrile seizures. 6. History of head trauma associated with loss of consciousness in the past 5 years or if the event occurred more than 5 years prior to screening and the subject has sequelae due to the event. 7. Evidence of untreated or inadequately treated sleep-disordered breathing including: a. Presence of clinically significant and untreated obstructive or central sleep apnea as determined by the Investigator or documented previously; or documentation of one of the following: b. Apnea index (AI) >10 if on OSA treatment or untreated; or c. Clinically significant hypoventilation; or d. Noncompliance with primary OSA therapy. (Compliance defined as positive airway pressure use of =4 hours per night on =70% of nights [=5 of 7 nights/week], historical report [with Investigator concurrence] of use of an oral appliance on =70% of nights [=5 of 7 nights/week], or receipt of an effective surgical intervention for OSA symptoms). 8. Parasomnias (e.g., sleep walking, REM Sleep Behavior Disorder, etc.) felt by the investigator to negatively affect the conduct of the study. Parasomnia events associated with physical injury to the subject (or others) shall be discussed with the Medical Monitor. 9. Meets criteria for current major depression by clinical interview. 10. Any other clinically relevant medical, behavioral, or psychiatric disorder other than narcolepsy that is associated with excessive sleepiness. 11. History or presence of bipolar disorder, bipolar related disorders, schizophrenia, schizophrenia spectrum disorders, or other psychotic disorders according to DSM-5 criteria. 12. History or presence of any unstable or clinically significant medical condition, behavioral or psychiatric disorder (including active suicidal ideation), or history or presence of another neurological disorder or surgical history that might affect the subject's safety and/or interfere with the conduct of the study in the opinion of the Investigator. 13. A current electrocardiogram (ECG) with clinically significant deviation(s) from normal, or clinically significant physical examination findings, as determined by the Investigator at screening. 14. Any current clinically significant laboratory abnormality as determined by the Investigator at screening. 15. Is a female subject who is pregnant, nursing or lactating. 16. A positive urine drug screen for benzodiazepines or drugs of abuse, a positive alcohol test, a history of substance abuse including alcohol abuse, or unwillingness to refrain from consuming alcohol during the study (if the subject takes prescribed amphetamines, a positive result for amphetamines will not exclude the subject). 17. Treatment with any central nervous system sedating agents including but not limited to
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of JZP-258 in the treatment of cataplexy in subjects with narcolepsy; Secondary Objective: Key Secondary Objective • To evaluate the efficacy of JZP-258 in the treatment of excessive daytime sleepiness (EDS) in subjects with narcolepsy. Secondary Objective • To evaluate the safety of JZP-258 in the treatment of subjects with narcolepsy with cataplexy. Exploratory Objective • To characterize the conversion from non-Xyrem anticataplectic treatment regimens to JZP-258 in subjects with narcolepsy with cataplexy. ;Primary end point(s): Change in weekly number of cataplexy attacks from the two weeks of the Stable-Dose Period to the two weeks of the Double-Blind Randomized-Withdrawal Period;Timepoint(s) of evaluation of this end point: End of stable-dose period to end of double- blind randomized-withdrawal period (2 weeks) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change in the Epworth Sleepiness Scale (ESS) score from the end of the Stable- Dose Period to the end of the Double-Blind Randomized-Withdrawal Period. • PGIc for narcolepsy overall at the end of the Double-Blind Randomized-Withdrawal Period. • CGIc for narcolepsy overall at the end of the Double-Blind Randomized-Withdrawal Period. • Change in QoL (SF-36) from the end of the Stable-Dose Period to the end of the Double-Blind Randomized-Withdrawal Period. • Change in QoL (EuroQol 5 Dimensions Self-Report Questionnaire) from the end of the Stable-Dose Period to the end of the Double-Blind Randomized- Withdrawal Period. ;Timepoint(s) of evaluation of this end point: End of stable-dose period to end of double-blind randomized-withdrawal period (2 weeks) | — |
Countries
Belgium, Croatia, Czech Republic, Denmark, Finland, France, Germany, Italy, Netherlands, Poland, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactMario D'Achille
Jazz Pharmaceuticals
Outcome results
None listed