A clinical trial undertaken around the world for treating excessive daytime sleepiness in subjects with obstructive sleep apnea. 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: 8 May 2017
• Main ID: EUCTR2014-005514-31-NL
• Date of registration: 19/06/2015
• Prospective Registration: Yes
• Primary sponsor: Jazz Pharmaceuticals Inc.
• Public title: A clinical trial undertaken around the world for treating excessive daytime sleepiness in subjects with obstructive sleep apnea. 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 Obstructive Sleep Apnea (OSA) -
• Date of first enrolment: 21/01/2016
• Target sample size: 440
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-005514-31
• 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: 5
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Canada, France, Germany, Netherlands, Sweden, United States

Contacts

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

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

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion Criteria:

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

1. Male or female between 18 and 75 years of age, inclusive.
2. Diagnosis of OSA according to ICSD-3 criteria.
3. Subject report (with clinician concurrence) of at least minimal use of a primary therapy for OSA or an attempt to use a primary therapy for OSA as follows:
a. Use of a primary therapy for OSA (i.e., positive airway pressure or oral appliance) on at least 1 night/week, or
b. History of at least 1 month of an attempt to use one or more primary OSA therapies with at least one documented adjustment that was made in an attempt to optimize the primary OSA therapy, or
c. History of a surgical intervention intended to treat OSA symptoms.
4. Subject report (with clinician concurrence) of a stable level of compliance with a primary OSA therapy for at least 1 month prior to Baseline as follows:
a. A stable level of use of a primary OSA therapy, or
b. A lack of use of a primary OSA therapy following a history of attempted use, or
c. A history of a surgical intervention intended to treat OSA symptoms.
5. Baseline Epworth Sleepiness Scale (ESS) score =10.
6. Baseline mean sleep latency =30 minutes as documented by the mean of the first four trials of the MWT.
7. Usual nightly total sleep time of at least 6 hours.
8. Body mass index from 18 to <45 kg/m2.
9. 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.
10. Willing and able to comply with the study design schedule and other requirements.
11. 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 396
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 44

Exclusion criteria:
Exclusion Criteria

Subjects who demonstrate any of the following will be excluded from the study.
1. Unwilling to attempt to use one or more primary OSA therapies.
2. Female subjects who are pregnant, nursing, or lactating.
3. Usual bedtime later than 1 AM (0100 hours).
4. Occupation requiring nighttime shift work or variable shift work.
5. Any other clinically relevant medical, behavioral, or psychiatric disorder other than 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.History or 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, safety, PK 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 any gastric bypass procedure.
9. Presence of renal impairment or calculated creatinine clearance <60 mL/min.
10. Clinical significant ECG abnormality, in the opinion of the Investigator
11. This criteria has been removed.
12. Presence of significant cardiovascular disease including but not limited to: myocardial infarction within the past year, unstable angina pectoris, symptomatic congestive heart failure (ACC/AHA stage C or D), revascularization procedures within the past year, ventricular cardiac arrhythmias requiring an automatic implantable cardioverter defibrillator (AICD) or medication therapy, uncontrolled hypertension, systolic blood pressure =155 mmHg or diastolic blood pressure =95 mmHg (at
screening, or consistently across Baseline measures according to protocol specifications), or any history of cardiovascular disease or any significant cardiovascular condition that in the investigator's opinion may jeopardize subject safety in the study.
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 or stimulants (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 a monoamine oxidase inhibitor (MAOI) in the past 14 days or five half-lives (whichever is longer) prior to the Baseline Visit, or plans to use an MAOI during the study.
17. Received an investigational drug in the past 30 days or five half-lives (whichever is longer) prior to the Baseline Visit, or plans to use an investigational drug (other than the study drug) during the study.

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

Health Condition(s) or Problem(s) studied

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

Treatment of excessive sleepiness in adult patients with obstructive sleep apnea; to increase the ability to stay awake throughout the day.
MedDRA version: 18.1 Level: HLT Classification code 10028716 Term: Narcolepsy and associated conditions System Organ Class: 100000004873

Intervention(s)

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: 357-
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: 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

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: 44.6-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To evaluate the efficacy of JZP-110 administered once daily for up to 12 weeks in doses of 37.5, 75, 150, and 300 mg compared to placebo in the treatment of excessive sleepiness in adult subjects with OSA.

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 Objective: To evaluate the safety and tolerability of JZP-110 administered once daily for up to 12 weeks in doses of 37.5, 75, 150, and 300 mg compared to placebo in the treatment of excessive sleepiness in adult subjects with OSA.
To characterize the pharmacokinetics (PK) of JZP-110 in subjects with OSA using sparse sampling methods.

Primary end point(s): Co-primary Efficacy Endpoints:

• 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 Outcome(s)

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 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
• EQ-5D-5L:
o 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
• Change in frequency of use of primary OSA therapy from Baseline to Week 12.
• Change in PSG parameters including total sleep time (TST), time in 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

Secondary ID(s)

14-003

2014-005514-31-DE

Source(s) of Monetary Support

Jazz Pharmaceuticals Inc.