A clinical trial undertaken around the world in adult patients with excessive daytime sleepiness . These patients are randomly given a drug or an inactive drug to increase their ability to stay awake throughout the day.

• Register: EUCTR
• Last refreshed on: 14 March 2016
• Main ID: EUCTR2014-005487-15-FR
• Date of registration: 24/06/2015
• Prospective Registration: Yes
• Primary sponsor: Jazz Pharmaceuticals Inc.
• Public title: A clinical trial undertaken around the world in adult patients with excessive daytime sleepiness . These patients are randomly given a drug or an inactive drug to increase their ability to stay awake throughout the day.
• Scientific title: A Twelve-week, Double-blind, Placebo-controlled, Randomized, Parallel-group, Multicenter Study of the Safety and Efficacy of JZP-110 [(R)-2-amino-3-phenylpropylcarbamate hydrochloride] in the Treatment of Excessive Sleepiness in Subjects with Narcolepsy
• Date of first enrolment: 08/12/2015
• Target sample size: 240
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-005487-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4

Countries of recruitment

Canada, Finland, France, Germany, Netherlands, United States

Contacts

• Name: Michael Nelson
• Affiliation: Jazz Pharmaceuticals Inc.

• Name: Michael Nelson
• Affiliation: Jazz Pharmaceuticals Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
Each subject must meet the following criteria to be enrolled in the study:

1. Males and females between 18 and 70 years of age, inclusive.
2. Diagnosis of narcolepsy according to ICSD-3 or DSM-5 criteria.
3. Baseline mean sleep latency =10 minutes as documented by the mean of the first four trials of the Baseline 5-trial MWT.
4. Baseline Epworth Sleepiness Scale (ESS) score =10.
5. Usual nightly total sleep time of at least 6 hours.
6. Body mass index from 18 to <40 kg/m2.
7. 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.
8. Willing and able to comply with the study design schedule and other requirements.
9. Willing and able to provide written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 223
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 17

Exclusion criteria:
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. Moderate or severe obstructive sleep apnea (OSA) on the baseline PSG.
5. Any other clinically relevant medical, behavioral, or psychiatric disorder other than narcolepsy 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 toDSM-5 criteria.
7. History or presence of any unstable or clinically significant 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, safety, or PK assessments per the judgment of the Investigator.
8. History of bariatric surgery within the past year.
9. Presence of renal impairment or calculated creatinine clearance <60 mL/min.
10. History or presence of a risk factor for torsade de pointes (e.g., clinically significant ECG abnormality, QTcF interval of >450 msec for males and >470 msec for females, hypokalemia, family history of long QT syndrome).
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 (whichever is longer) prior to the Baseline visit.
12. History or presence of significant cardiovascular disease including but not limited to: myocardial infarction, uncontrolled hypertension, systolic blood pressure =140 mmHg or diastolic blood pressure =90 mmHg (at screening, or consistently across Baseline measures according to protocol specifications), angina pectoris, clinically significant arrhythmias, clinically significant valvular heart disease, history of any revascularization procedures or second or third degree heart block with/without a pacemaker, or heart failure.
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 Baseline assessments or anticipated excessive use during the study defined as >600 mg/day of caffeine.
15. Use of any over-the-counter (OTC) or prescription medications that could affect the evaluation of excessive sleepiness within 7 days prior to the Baseline visit, or planned use of such drug(s) at some point throughout the duration of the study. Examples of excluded medications include OTC sleep aids orstimulants (e.g., pseudoephedrine), methylphenidate, amphetamines, modafinil, armodafinil, sodium oxybate, pemoline, trazodone, hypnotics, benzodiazepines, barbiturates, and opioids. 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.
16. Use of any medications that could affect the evaluation of cataplexy within 7 days prior to the Baseline visit, or planned use of such drug(s) at some point throughout the duration of the study. Examples of excluded anti-cataplectic medications include selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Treatment of excessive sleepiness in adult patients with narcolepsy
MedDRA version: 18.0 Level: HLT Classification code 10028716 Term: Narcolepsy and associated conditions System Organ Class: 100000004873

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: (R)-2-amino-3-phenylpropylcarbamate hydrochloride
Product Code: JZP-110
Pharmaceutical Form: Capsule
INN or Proposed INN: Not yet available
CAS Number: 178429-65-7
Current Sponsor code: JZP-110
Other descriptive name: JZP-110
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 357.0-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Name: (R)-2-amino-3-phenylpropylcarbamate hydrochloride
Product Code: JZP110
Pharmaceutical Form: Capsule
INN or Proposed INN: Not yet available
CAS Number: 178429-65-7
Current Sponsor code: JZP110
Other descriptive name: JZP-110
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 178.5-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Name: (R)-2-amino-3-phenylpropylcarbamate hydrochloride
Product Code: JZP110
Pharmaceutical Form: Capsule
INN or Proposed INN: Not yet available
CAS Number: 178429-65-7
Current Sponsor code: JZP-110
Other descriptive name: JZP-110
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 89.3-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Efficacy Endpoints

Co-primary Efficacy Endpoint:

• MWT: Change in the mean sleep latency time (in minutes) as determined from the first four trials of a 40-minute MWT from Baseline to Week 12

• ESS: Change in ESS score from Baseline to Week 12

Secondary Objective: To evaluate the safety and tolerability of JZP-110 administered once daily for up to 12 weeks in doses of 75, 150, and 300 mg compared to placebo in the treatment of excessive sleepiness in adult subjects with narcolepsy.
To characterize the pharmacokinetics (PK) of JZP-110 in subjects with narcolepsy using sparse sampling methods.

Timepoint(s) of evaluation of this end point: During the Treatment Phase, subjects will return to the investigative site to complete efficacy and safety assessments at the end of Weeks 1, 4, 8, and 12

Main Objective: To evaluate the efficacy of JZP-110 administered once daily for up to 12 weeks in doses of 75, 150, and 300 mg compared to placebo in the treatment of excessive sleepiness in adult subjects with narcolepsy.

Secondary Outcome(s)

Secondary end point(s): Key Secondary Efficacy Endpoint:

• PGIc: Percentage of subjects reported as improved (minimally, much, or very much) on the PGIc at Week 12

Other Secondary Endpoints:

• Time course of efficacy on the MWT: Change in sleep latency time (in minutes) on each of the 5 MWT trials
• CGIc: Percentage of subjects reported as improved (minimally, much, or very much) at Week 12
• MWT: Change in the mean sleep latency time (in minutes) as determined from the first four trials of a 40-minute MWT from Baseline to Week 1 and Week 4
• ESS: Change in ESS score from Baseline to Week 1, Week 4, and Week 8
• PGIc: Percentage of subjects reported as improved at Week 1, Week 4, and Week 8
• CGIc: Percentage of subjects reported as improved at Week 1, Week 4, and Week 8

Functional Outcomes and Quality of Life Endpoints
• FOSQ-10: Change in the total score from Baseline to Week 1, Week 4, Week 8, and Week 12
• SF-36v2: Change in the total score and change in the 8 subscales from Baseline to Week 4, Week 8, and Week 12
o EQ-5D-5L: EQ-5D Dimensions:
?• Number and percentage of subjects in each of the 5 levels (e.g., no problem, slight problem, moderate problem, severe problem, unable) for each dimension (e.g., mobility, self-care) over time
?• Number and percentage of subjects reporting any problems (levels 2-5) for each dimension (e.g., mobility, self-care) over time
o EQ VAS: Mean and SD or median with 25th and 75th percentiles for the VAS at Baseline, Week 1, Week 4, Week 8 and Week 12. Change in the mean VAS scores from Baseline to Week 1, Week 4, Week 8, and Week 12
o EQ-5D-5L Index: Index value at Baseline to Week 1, Week 4, Week 8, and Week 12
• WPAI:SHP: Percent work time missed due to problem over time, percent impairment while working due to problem over time, percent overall work impairment due to problem over time, and percent activity impairment due to problem over time

Exploratory Endpoints
• Number of Cataplexy Attacks: Change in the mean weekly number of cataplexy attacks in the subset of subjects who report the presence of cataplexy at randomization from Baseline to Week 1, Week 4, Week 8, and Week 12
• Change in PSG parameters including total sleep time (TST), Stages N1, N2, N3, wake after sleep onset (WASO), number of awakenings, AI, AHI, number of central apneas, SaO2 nadir, and SaO2 mean from Baseline to Week 1, Week 4, and Week 12.

Safety Endpoints
To evaluate the safety and tolerability evaluations as determined by the occurrence of and/or changes in:
• Treatment-emergent adverse events
• Change in clinical laboratory tests (chemistry, hematology, and urinalysis)
• Vital signs
• 24 hour ambulatory blood pressure monitoring
• 12-lead electrocardiograms (ECGs)
• Physical examination
• C-SSRS

Timepoint(s) of evaluation of this end point: During the Treatment Phase, subjects will return to the investigative site to complete efficacy and safety assessments at the end of Weeks 1, 4, 8, and 12

Secondary ID(s)

14-002

2014-005487-15-DE

Source(s) of Monetary Support

Jazz Pharmaceuticals Inc.