| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Treatment of excessive sleepiness in adult patients with narcolepsy or obstructive sleep apnea; to increase the ability to stay awake throughout the day. |
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| E.1.1.1 | Medical condition in easily understood language |
| Treatment of excessive sleepiness in adult patients with narcolepsy or obstructive sleep apnea; to increase the ability to stay awake throughout the day. |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 19.1 |
| E.1.2 | Level | HLT |
| E.1.2 | Classification code | 10028716 |
| E.1.2 | Term | Narcolepsy and associated conditions |
| E.1.2 | System Organ Class | 100000004873 |
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| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the safety and tolerability of JZP-110 administered once daily for up to 52 weeks in doses of 75, 150, and 300 mg. |
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| E.2.2 | Secondary objectives of the trial |
| To evaluate the maintenance of efficacy of JZP-110 administered once daily for up to 52 weeks in doses of 75, 150, and 300 mg in the treatment of excessive sleepiness in adult subjects with narcolepsy or obstructive sleep apnea (OSA). |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Inclusion Criteria:
All subjects must meet the following criteria to be enrolled in the study.
1. Subject meets one of the following:
a. Completed Study 14-002 or 14-003 (Group A)
b. Completed Study 14-004, 15-004, 15-005, ADX-N05 201 or ADX-N05 202 (Group B)
2. Subject is able, in the opinion of the investigator, to take JZP-110 for 40 weeks if continuing from 14-002 or 14-003 or for 52 weeks if thesubject completed 14-004, 15-004, 15-005, ADX-N05 201, or ADX-N05 202, and is able to complete all tests and visits described in this protocol.
3. Usual nightly total sleep time of at least 6 hours.
4. Body mass index from 18 to <45 kg/m2.
5. Consent to use a medically acceptable method of contraception for at least 2 months prior to the first dose of study drug, throughout the entire study period, and for 30 days after the study is completed.
6. Willing and able to comply with the study design schedule and other requirements.
7. Willing and able to provide written informed consent.
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| E.4 | Principal exclusion criteria |
Exclusion Criteria:
Subjects who demonstrate any of the following will be excluded from the study.
1. Female subjects who are pregnant, nursing, or lactating.
2. Usual bedtime later than 1 AM (0100 hours).
3. Occupation requiring nighttime or variable shift work.
4. Experienced any serious adverse event (SAE) in a previous study that was deemed related to JZP-110 or experienced an AE in a previous study that might prevent him/her from safely participating in and completing the current study.
5. Any other clinically relevant medical, behavioral, or psychiatric disorder other than narcolepsy or OSA that is associated with excessive sleepiness.
6. History or presence of bipolar disorder, bipolar related disorders, schizophrenia, schizophrenia spectrum disorders, or other psychotic disorders according to DSM-5 criteria.
7. Presence of any acutely unstable medical condition, behavioral or psychiatric disorder (including active suicidal ideation), or surgical history that could affect the safety of the subject or interfere with study efficacy or safety assessments, or the ability of the subject to complete the trial per the judgment of the Investigator.
8. History of bariatric surgery within the past year or a history of gastric bypass procedure
9. Presence of renal impairment or calculated creatinine clearance <60 mL/min.
10. Clinically significant ECG abnormality in the opinion of the Investigator.
11. Use of concomitant medication with known risk for torsade de pointes (e.g., citalopram, escitalopram, azithromycin, clarithromycin, erythromycin, levofloxacin, moxifloxacin, ondansetron, pimozide, thioridazine) within 14 days or 5 half-lives of the drug (whichever is longer) before administration of the first dose of the study drug.
12. Presence or history of significant cardiovascular disease including but not limited to: myocardial infarction within the past year, uncontrolled hypertension, systolic blood pressure =155 mmHg or diastolic blood pressure =95 mmHg (at screening or Baseline according to protocol specifications), unstable angina pectoris, congestive heart failure, chronic ventricular arrhythmias, or history of any revascularization procedures within the past year.
13. Laboratory value(s) outside the laboratory reference range that are considered to be clinically significant by the Investigator (clinical chemistry, hematology, and urinalysis); NOTE: Screening labs may be repeated once.
14. Excessive caffeine use one week prior to the Baseline Visit or anticipated excessive use during the study defined as >600 mg/day of caffeine.
15. Use of a monoamine oxidase inhibitor (MAOI) in the past 14 days or five half-lives of the drug (whichever is longer) prior to the Baseline Visit, or plans to use an MAOI during the study.
16. Received an investigational drug other than JZP-110 in the past 30 days or five half-lives (whichever is longer) before the Baseline Visit, or plans to use an investigational drug (other than the study drug) during the study.
17. Current or past (within the past 2 years) diagnosis of a moderate or severe substance use disorder according to DSM-5 criteria.
18. Nicotine dependence that has an effect on sleep (e.g., a subject who routinely awakens at night to smoke).
19. Current, past (within the past 2 years), or seeking treatment for a substance related disorder.
20. Urine drug screen positive for an illicit drug of abuse (including cannabinoids) at screening or at any point throughout the duration of the study, except for a prescribed drug (e.g., amphetamine) at screening.
21. History of phenylketonuria (PKU) or history of hypersensitivity to phenylalanine-derived products.
22. Group A: Planned use of any over-the-counter (OTC) or prescription medications that could affect the evaluation of excessive sleepiness at any time during the study.
Group B: Use of any over-the-counter (OTC) or prescription medications that could affect the evaluation of excessive sleepiness within within a time period prior to the Baseline Visit corresponding to at least five half-lives of the drug(s) at some point throughout the duration of the study. Medications should be discontinued such that the subject has returned to his/her baseline level of daytime sleepiness at least 7 days prior to the Baseline Visit, in the opinion of the Investigator.
Examples of excluded medications include OTC sleep aids or stimulants (e.g., pseudoephedrine), methylphenidate, amphetamines, modafinil, armodafinil, sodium oxybate, pemoline, trazodone, hypnotics, benzodiazepines, barbiturates, and opioids.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Efficacy endpoints (ESS, PGIc, CGIc) will be summarized by treatment using descriptive statistics. ESS data will be compared to baseline data from this study for subjects in Group B and to baseline data from the previous trial that the subject had participated in for Group A. The outcome measures in the FOSQ-10, SF-36v2, and EQ-5D-5L will be summarized and displayed graphically. No adjustment of significance level for multiple testing will be employed.
Safety and tolerability evaluations will consist of treatment-emergent adverse events (TEAEs) and changes in clinical laboratory tests (chemistry, hematology, and urinalysis), vital signs, 12-lead electrocardiograms (ECGs), physical exams, and the C SSRS assessments. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Group A: Visits 6, 9, 12 and 15 (as shown in Appendix 1 in the protocol)
Group B: Baseline, visits 7, 10, 13, 16, 19 (as shown in Appendix 2 in the protocol)
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| E.5.2 | Secondary end point(s) |
The outcome measures associated with the WPAI:SHP and the Resource Utilization Questionnaire will be summarized by final dose and time point and displayed graphically. For subjects who participated in Study 14-002 or 14-003, the WPAI:SHP measures may also be summarized by the previous treatment group. Where applicable, the changes in the WPAI:SHP measures from prior study baseline and from the endpoint of the prior study will be examined.
Standard unit costs will be applied to the resources identified with the Resource Utilization Questionnaire (as well as to any hospitalizations reported as SAEs) in order to calculate the mean/median healthcare costs over the one-year period.
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Group A: Visits 9, 12 and 15 (as shown in Appendix 1 in the protocol)
Group B: Baseline, visits 10, 13, 16, 19 (as shown in Appendix 2 in the protocol) |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | Yes |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 27 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Canada |
| Finland |
| France |
| Germany |
| Netherlands |
| Sweden |
| United States |
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| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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