Twelve-week Study of the Safety and Efficacy of JZP-110 in the Treatment of Excessive Sleepiness in Narcolepsy

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02348593

Enrollment

239

Registered

2015-01-28

Start date

2015-05-31

Completion date

2017-02-28

Last updated

2019-07-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Narcolepsy

Brief summary

This trial is a 12-week, randomized, double-blind, placebo controlled, multicenter, 4-treatment parallel group study of the safety and efficacy of JZP-110 in the treatment of excessive sleepiness in adult subjects with narcolepsy.

Interventions

DRUGJZP-110

DRUGPlacebo oral tablet

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Inclusion criteria

Major Inclusion Criteria: 1. Males and females between 18 and 75 years of age, inclusive 2. Diagnosis of narcolepsy according to ICSD-3 or DSM-5 criteria 3. Body mass index from 18 to \<45 kg/m2 4. Consent to use a medically acceptable method of contraception 5. Willing and able to provide written informed consent Major

Exclusion criteria

1. Female subjects who are pregnant, nursing, or lactating 2. Moderate or severe sleep apnea on the baseline PSG. 3. Any other clinically relevant medical, behavioral, or psychiatric disorder other than narcolepsy that is associated with excessive sleepiness 4. History or presence of bipolar disorder, bipolar related disorders, schizophrenia, schizophrenia spectrum disorders, or other psychotic disorders according to DSM-5 criteria 5. 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 6. History of bariatric surgery within the past year or a history of any gastic bypass procedure 7. Presence or history of significant cardiovascular disease 8. Use of any over-the-counter (OTC) or prescription medications that could affect the evaluation of excessive sleepiness 9. Use of any medications that could affect the evaluation of cataplexy 10. Received an investigational drug in the past 30 days or five half-lives (whichever is longer) 11. Previous exposure to or participation in a previous clinical trial of JZP-110 (ADX-N05, R228060, YKP10A) 12. History of phenylketonuria (PKU) or history of hypersensitivity to phenylalanine-derived products

Design outcomes

Primary

Measure	Time frame	Description
Change in Maintenance of Wakefulness Test (MWT) From Baseline to Week 12	Baseline to Week 12	Change in mean sleep latency time (in minutes) as determined from the first 4 trials of a 40-minute MWT from baseline to Week 12. MWT sleep latency ranges from 0 to 40 minutes, with higher scores indicating greater ability to stay awake; a positive change from baseline represents improvement in the sleep latency time. Mean sleep latency defined as the average of the first 4 MWT trials, if 3 or 4 of them are non-missing.
Change in ESS Score From Baseline to Week 12	Baseline to Week 12	Change in Epworth Sleepiness Scale (ESS) score from Baseline to Week 12. A negative change from baseline represents improvement in excessive sleepiness. The ESS is a self-administered questionnaire with 8 questions. Each activity is scored on a scale ranging from 0-3, with 0 = would never fall asleep, and 3 = high chance of falling asleep. The total score ranges from 0-24, with a higher number representing an increased propensity for sleepiness. An analysis of covariance (ANCOVA) was used for the analysis of ESS scores. The response variable was the change in ESS score from baseline.

Secondary

Measure	Time frame	Description
Change in Sleep Latency Time on MWT Trial 5 at Week 12	Change from baseline for sleep latency in MWT during trial 5 at week 12	Time course of efficacy in MWT: Change in sleep latency (in minutes) on each of the 5 MWT trials at Week 12.
Subjects Reported Improved on the Patient Global Impression of Change (PGIc) at Week 12	Baseline to Week 12	Percentage of subjects reported as improved (minimally, much, or very much) on the PGIc at Week 12. PGIc was rated by subjects and measures the change in their condition since treatment starts on a 7-point scale ranging from 1= very much improved to 7= very much worse
Change in Sleep Latency Time on MWT Trial 1 at Week 12	Change from baseline for sleep latency in MWT during trial 1 at week 12	Time course of efficacy in MWT: Change in sleep latency (in minutes) on each of the 5 MWT trials at Week 12.
Change in Sleep Latency Time on MWT Trial 2 at Week 12	Change from baseline for sleep latency in MWT during trial 2 at week 12	Time course of efficacy in MWT: Change in sleep latency (in minutes) on each of the 5 MWT trials at Week 12.
Change in Sleep Latency Time on MWT Trial 3 at Week 12	Change from baseline for sleep latency in MWT during trial 3 at week 12	Time course of efficacy in MWT: Change in sleep latency (in minutes) on each of the 5 MWT trials at Week 12.
Change in Sleep Latency Time on MWT Trial 4 at Week 12	Change from baseline for sleep latency in MWT during trial 4 at week 12	Time course of efficacy in MWT: Change in sleep latency (in minutes) on each of the 5 MWT trials at Week 12.
Change in the Mean Sleep Latency Time as Determined From the First 4 Trials of a 40-Minute MWT From Baseline to Week 4	Baseline to Week 4	Change in mean sleep latency time (in minutes) as determined from the first 4 trials of a 40-minute MWT from Baseline to Week 4.

Countries

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

Participant flow

Pre-assignment details

239 subjects were randomized in a 1:1:1:1 ratio to receive placebo, 75 mg JZP-110, 150 mg JZP-110 or 300 mg JZP-110. 236 subjects received at least 1 dose of study medication and comprised the Safety Population; the remaining 3 subjects were randomized in error (did not receive study medication) and were excluded from the Safety Population.

Participants by arm

Arm	Count
75 mg of JZP-110 75 mg JZP-110 administered orally, QD, for the 12-week treatment phase.	59
150 mg JZP-110 Subjects randomized to receive 150 mg JZP-110 initially received 75 mg JZP-110 from Day 1 through Day 3 of the Treatment Phase and then received 150 mg JZP-110 starting on Day 4, administered orally, QD.	59
300 mg of JZP-110 Subjects randomized to receive 300 mg JZP-110 initially received 150 mg JZP-110 from Day 1 through Day 3 of the Treatment Phase, and received 300 mg JZP-110 starting on Day 4, administered orally, QD.	59
Placebo Placebo administered orally, QD, for the 12 week treatment phase.	59
Total	236

Baseline characteristics

Characteristic	75 mg of JZP-110	Total	Placebo	300 mg of JZP-110	150 mg JZP-110
Age, Continuous	36.5 years STANDARD_DEVIATION 12.78	36.3 years STANDARD_DEVIATION 12.47	36.0 years STANDARD_DEVIATION 15.17	34.3 years STANDARD_DEVIATION 11.51	38.1 years STANDARD_DEVIATION 13
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	2 Participants	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Asian	0 Participants	6 Participants	0 Participants	3 Participants	3 Participants
Race (NIH/OMB) Black or African American	12 Participants	33 Participants	10 Participants	5 Participants	6 Participants
Race (NIH/OMB) More than one race	1 Participants	5 Participants	2 Participants	1 Participants	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	46 Participants	189 Participants	47 Participants	48 Participants	48 Participants
Sex: Female, Male Female	37 Participants	154 Participants	35 Participants	40 Participants	42 Participants
Sex: Female, Male Male	22 Participants	82 Participants	24 Participants	19 Participants	17 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 59	0 / 59	0 / 59	0 / 59
other Total, other adverse events	17 / 59	19 / 59	32 / 59	36 / 59
serious Total, serious adverse events	0 / 59	0 / 59	1 / 59	0 / 59

Outcome results

Primary

Change in ESS Score From Baseline to Week 12

Change in Epworth Sleepiness Scale (ESS) score from Baseline to Week 12. A negative change from baseline represents improvement in excessive sleepiness. The ESS is a self-administered questionnaire with 8 questions. Each activity is scored on a scale ranging from 0-3, with 0 = would never fall asleep, and 3 = high chance of falling asleep. The total score ranges from 0-24, with a higher number representing an increased propensity for sleepiness. An analysis of covariance (ANCOVA) was used for the analysis of ESS scores. The response variable was the change in ESS score from baseline.

Time frame: Baseline to Week 12