Trial Outcomes & Findings for A Study of the Efficacy and Safety of JZP-258 in Subjects With Narcolepsy With Cataplexy (NCT NCT03030599)
NCT ID: NCT03030599
Last Updated: 2020-11-12
Results Overview
Participants completed a daily Cataplexy Frequency Diary each night prior to bedtime. Participants were to record the number of cataplexy attacks that they had each day.
COMPLETED
PHASE3
201 participants
Change from baseline (2 weeks of the Stable Dose Period) to the 2 weeks of the Double Blind Randomized Withdrawal Period (DB RWP)
2020-11-12
Participant Flow
Subjects were evaluated for eligibility during the Screening Period (up to 30 days).
Participant milestones
| Measure |
Open-label JZP-258
All 201 subjects entered the Open Label Optimized Treatment and Titration Period (OL OTTP) and received at least 1 dose of study drug. During the OL OTTP (12 weeks), eligible subjects were transitioned to JZP-258 treatment based on their pre-treatment status. During the Stable Dose Period, subjects received open-label JZP-258 at the same unchanged dose that they received during the last 2 weeks of the Open Label Treatment and Titration Period.
|
JZP-258
JZP-258 at the dose taken during the last 2 weeks of the Stable Dose Period.
|
Placebo
A matching oral solution to JZP-258.
|
|---|---|---|---|
|
Open Label Treatment and Titration
STARTED
|
201
|
0
|
0
|
|
Open Label Treatment and Titration
COMPLETED
|
155
|
0
|
0
|
|
Open Label Treatment and Titration
NOT COMPLETED
|
46
|
0
|
0
|
|
Stable Dose
STARTED
|
149
|
0
|
0
|
|
Stable Dose
COMPLETED
|
144
|
0
|
0
|
|
Stable Dose
NOT COMPLETED
|
5
|
0
|
0
|
|
Double Blind Randomized Withdrawal
STARTED
|
0
|
69
|
67
|
|
Double Blind Randomized Withdrawal
COMPLETED
|
0
|
69
|
59
|
|
Double Blind Randomized Withdrawal
NOT COMPLETED
|
0
|
0
|
8
|
|
Open-label Extension
STARTED
|
74
|
0
|
0
|
|
Open-label Extension
COMPLETED
|
67
|
0
|
0
|
|
Open-label Extension
NOT COMPLETED
|
7
|
0
|
0
|
Reasons for withdrawal
| Measure |
Open-label JZP-258
All 201 subjects entered the Open Label Optimized Treatment and Titration Period (OL OTTP) and received at least 1 dose of study drug. During the OL OTTP (12 weeks), eligible subjects were transitioned to JZP-258 treatment based on their pre-treatment status. During the Stable Dose Period, subjects received open-label JZP-258 at the same unchanged dose that they received during the last 2 weeks of the Open Label Treatment and Titration Period.
|
JZP-258
JZP-258 at the dose taken during the last 2 weeks of the Stable Dose Period.
|
Placebo
A matching oral solution to JZP-258.
|
|---|---|---|---|
|
Open Label Treatment and Titration
Protocol deviation
|
8
|
0
|
0
|
|
Open Label Treatment and Titration
Other
|
1
|
0
|
0
|
|
Open Label Treatment and Titration
Physician Decision
|
3
|
0
|
0
|
|
Open Label Treatment and Titration
Lack of Efficacy
|
1
|
0
|
0
|
|
Open Label Treatment and Titration
Non-Compliance with Study Drug
|
4
|
0
|
0
|
|
Open Label Treatment and Titration
Adverse Event
|
18
|
0
|
0
|
|
Open Label Treatment and Titration
Withdrawal by Subject
|
6
|
0
|
0
|
|
Open Label Treatment and Titration
Sponsor decision
|
2
|
0
|
0
|
|
Open Label Treatment and Titration
Lost to Follow-up
|
3
|
0
|
0
|
|
Stable Dose
Protocol deviation
|
3
|
0
|
0
|
|
Stable Dose
Adverse Event
|
1
|
0
|
0
|
|
Stable Dose
Lost to Follow-up
|
1
|
0
|
0
|
|
Double Blind Randomized Withdrawal
Lack of Efficacy
|
0
|
0
|
2
|
|
Double Blind Randomized Withdrawal
Adverse Event
|
0
|
0
|
3
|
|
Double Blind Randomized Withdrawal
Randomized in error
|
0
|
0
|
2
|
|
Double Blind Randomized Withdrawal
Withdrawal by Subject
|
0
|
0
|
1
|
|
Open-label Extension
Adverse Event
|
3
|
0
|
0
|
|
Open-label Extension
Lost to Follow-up
|
2
|
0
|
0
|
|
Open-label Extension
Lack of Efficacy
|
1
|
0
|
0
|
|
Open-label Extension
Other Reason
|
1
|
0
|
0
|
Baseline Characteristics
A Study of the Efficacy and Safety of JZP-258 in Subjects With Narcolepsy With Cataplexy
Baseline characteristics by cohort
| Measure |
Open Label Treatment and Titration
n=201 Participants
All 201 subjects entered the Open Label Optimized Treatment and Titration Period (OL OTTP) and received at least 1 dose of study drug. During the OL OTTP (12 weeks), eligible subjects were transitioned to JZP-258 treatment based on their pre-treatment status. During the Stable Dose Period, subjects received open-label JZP-258 at the same unchanged dose that they received during the last 2 weeks of the Open Label Treatment and Titration Period.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
195 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
122 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
79 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
177 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
8 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Change from baseline (2 weeks of the Stable Dose Period) to the 2 weeks of the Double Blind Randomized Withdrawal Period (DB RWP)Population: The efficacy population contains all randomized subjects who received at least one dose of double-blind study drug and had at least one set of post-randomization efficacy data.
Participants completed a daily Cataplexy Frequency Diary each night prior to bedtime. Participants were to record the number of cataplexy attacks that they had each day.
Outcome measures
| Measure |
JZP-258
n=69 Participants
JZP-258 at the dose taken during the last 2 weeks of the Stable Dose Period.
|
Placebo
n=65 Participants
A matching oral solution to JZP-258.
|
|---|---|---|
|
Change in Weekly Number of Cataplexy Attacks
|
0.00 attacks
Interval -0.49 to 1.75
|
2.35 attacks
Interval 0.0 to 11.61
|
SECONDARY outcome
Timeframe: From the end of the Stable Dose Period to the end of the Double Blind Randomized Withdrawal PeriodPopulation: The efficacy population contains all randomized subjects who received at least one dose of double-blind study drug and had at least one set of post-randomization efficacy data.
This is the key secondary endpoint. The Epworth Sleepiness Scale (ESS) was a self-administered questionnaire with 8 questions. Participants were asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. Most participants engaged in those activities at least occasionally, although not necessarily every day. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that participants average sleep propensity in daily life (ASP), or their 'daytime sleepiness'.
Outcome measures
| Measure |
JZP-258
n=69 Participants
JZP-258 at the dose taken during the last 2 weeks of the Stable Dose Period.
|
Placebo
n=65 Participants
A matching oral solution to JZP-258.
|
|---|---|---|
|
Change in the Epworth Sleepiness Scale (ESS) Score
|
0.00 score on a scale
Interval -1.0 to 1.0
|
2.0 score on a scale
Interval 0.0 to 5.0
|
SECONDARY outcome
Timeframe: At the end of the Double Blind Randomized Withdrawal PeriodPopulation: The efficacy population contains all randomized subjects who received at least one dose of double-blind study drug and had at least one set of post-randomization efficacy data.
At the end of the Double Blind Randomized Withdrawal Period (DB RWP), participants rated the change in their condition on a 7-point scale ranging from 1 = "very much improved" to 7 = "very much worse" since the last visit. This endpoint measures the percentage of participants with worsening PGIc scores for narcolepsy overall (defined as scores of Much Worse or Very Much Worse).
Outcome measures
| Measure |
JZP-258
n=69 Participants
JZP-258 at the dose taken during the last 2 weeks of the Stable Dose Period.
|
Placebo
n=65 Participants
A matching oral solution to JZP-258.
|
|---|---|---|
|
Number of Participants With Worsening Patient Global Impression of Change (PGIc) for Narcolepsy Overall
|
3 Participants
|
29 Participants
|
SECONDARY outcome
Timeframe: At the end of the Double Blind Randomized Withdrawal PeriodPopulation: The efficacy population contains all randomized subjects who received at least one dose of double-blind study drug and had at least one set of post-randomization efficacy data.
At the end of the Double Blind Randomized Withdrawal Period, Investigators rated their impression of any change in the severity of the participant's narcolepsy overall condition since the start of the Double Blind Randomized Withdrawal Period on a 7-point scale ranging from 1 = "very much improved" to 7 = "very much worse". This endpoint measures the percentage of participants with worsening CGIc scores for narcolepsy overall, defined as scores of Much Worse or Very Much Worse.
Outcome measures
| Measure |
JZP-258
n=68 Participants
JZP-258 at the dose taken during the last 2 weeks of the Stable Dose Period.
|
Placebo
n=65 Participants
A matching oral solution to JZP-258.
|
|---|---|---|
|
Number of Participants With Worsening Clinical Global Impression of Change (CGIc) for Narcolepsy Overall
|
4 Participants
|
39 Participants
|
SECONDARY outcome
Timeframe: At the End of the Stable Dose Period to the End of the Double Blind Randomized Withdrawal PeriodPopulation: The efficacy population contains all randomized subjects who received at least one dose of double-blind study drug and had at least one set of post-randomization efficacy data.
The SF-36v2 is a multi-purpose, short-form health survey with 36 questions/ items. It yields an 8-scale profile of functional health and well-being scores as well as a psychometrically-based physical and mental overall component summary measures. Two summary scores were derived using the SF-36v2. Physical Component Summary measures dimensions of functional health that are meaningful to respondents, including the impact of health and health-related changes on physical function, pain, and the ability to carry out daily roles. The Mental Component Summary component scale measures the impact of health and health-related changes on well-being, including vitality, social function, and emotional well-being. Participants self-report on items in a summary that have between 2-6 choices per item (e.g. none of the time, some of the time, etc.). Summations of item scores were transformed into a range from 0 to 100; zero= worst HRQL, 100=best HRQL. Higher scores indicate better health status.
Outcome measures
| Measure |
JZP-258
n=67 Participants
JZP-258 at the dose taken during the last 2 weeks of the Stable Dose Period.
|
Placebo
n=65 Participants
A matching oral solution to JZP-258.
|
|---|---|---|
|
Change in 36-Item Short Form Health Survey Version 2 (SF-36v2) Scores
Physical Component Summary
|
-0.03 score on a scale
Interval -2.07 to 2.41
|
-1.92 score on a scale
Interval -3.46 to 1.73
|
|
Change in 36-Item Short Form Health Survey Version 2 (SF-36v2) Scores
Mental Component Summary
|
1.55 score on a scale
Interval -1.88 to 3.78
|
-1.92 score on a scale
Interval -6.28 to 1.34
|
SECONDARY outcome
Timeframe: At the End of the Stable Dose Period to the End of the Double Blind Randomized Withdrawal PeriodPopulation: There were 68 JZP-258 participants included in the Crosswalk Index, and 69 JZP-258 participants in the VAS Score. The efficacy population contains all randomized subjects who received at least one dose of double-blind study drug and had at least one set of post-randomization efficacy data.
The EQ-5D-5L is a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/ discomfort, and anxiety/ depression). The EQ-5D-5L includes 5 levels of severity for each of the 5 dimensions of the descriptive system (1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems) that reflect increasing levels of difficulty. The 5 digit health states for each dimension are converted into a single value per country (0= equivalent to death, 1= equivalent to best imaginable health and values below 0= health states rated worse than death capped at -1), using the EQ-5D-5L crosswalk index value calculator as recommended by EuroQol group. A visual analogue scale (VAS) used within this scale recorded the participants self-rated health on a VAS and the endpoints resulted in a numeric value set ranging from 0 (= worst imaginable health state) up to 100 (= best imaginable health state).
Outcome measures
| Measure |
JZP-258
n=69 Participants
JZP-258 at the dose taken during the last 2 weeks of the Stable Dose Period.
|
Placebo
n=65 Participants
A matching oral solution to JZP-258.
|
|---|---|---|
|
Change in 5-level EQ-5D (EQ-5D-5L) Crosswalk Index Score and Visual Analog Scale
Crosswalk index
|
0.00 score on a scale
Interval -0.01 to 0.03
|
0.00 score on a scale
Interval -0.05 to 0.03
|
|
Change in 5-level EQ-5D (EQ-5D-5L) Crosswalk Index Score and Visual Analog Scale
VAS Score
|
0.00 score on a scale
Interval 0.0 to 5.0
|
-5.00 score on a scale
Interval -10.0 to 5.0
|
Adverse Events
JZP-258
Placebo
Serious adverse events
| Measure |
JZP-258
n=201 participants at risk
JZP-258 at the dose taken during the last 2 weeks of the Stable Dose Period.
|
Placebo
n=65 participants at risk
A matching oral solution to JZP-258.
|
|---|---|---|
|
Injury, poisoning and procedural complications
Accidental overdose
|
0.50%
1/201 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
0.00%
0/65 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
|
Investigations
Muscle enzyme increased
|
0.00%
0/201 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
1.5%
1/65 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Invasive ductal breast carcinoma
|
0.50%
1/201 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
0.00%
0/65 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
|
Nervous system disorders
Peripheral nerve paresis
|
0.50%
1/201 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
0.00%
0/65 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
|
Psychiatric disorders
Confusional state
|
0.50%
1/201 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
0.00%
0/65 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
|
Hepatobiliary disorders
Bile duct stone
|
0.50%
1/201 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
0.00%
0/65 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
|
Infections and infestations
Influenza
|
0.00%
0/201 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
1.5%
1/65 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
|
Infections and infestations
Viral cardiomyopathy
|
0.50%
1/201 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
0.00%
0/65 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
|
Psychiatric disorders
Hallucination
|
0.50%
1/201 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
0.00%
0/65 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
Other adverse events
| Measure |
JZP-258
n=201 participants at risk
JZP-258 at the dose taken during the last 2 weeks of the Stable Dose Period.
|
Placebo
n=65 participants at risk
A matching oral solution to JZP-258.
|
|---|---|---|
|
Nervous system disorders
Cataplexy
|
10.4%
21/201 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
7.7%
5/65 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
|
Nervous system disorders
Dizziness
|
11.4%
23/201 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
0.00%
0/65 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
|
Nervous system disorders
Headache
|
22.4%
45/201 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
1.5%
1/65 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
|
Nervous system disorders
Somnolence
|
2.5%
5/201 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
9.2%
6/65 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
|
Gastrointestinal disorders
Diarrhoea
|
6.5%
13/201 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
0.00%
0/65 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
|
Gastrointestinal disorders
Nausea
|
13.4%
27/201 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
0.00%
0/65 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
7.5%
15/201 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
1.5%
1/65 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
|
Infections and infestations
Influenza
|
8.5%
17/201 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
1.5%
1/65 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
|
Infections and infestations
Nasopharyngitis
|
9.5%
19/201 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
3.1%
2/65 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
|
Infections and infestations
Upper respiratory tract infection
|
5.5%
11/201 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
0.00%
0/65 • Through week 18 or early termination.
Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.
|
Additional Information
Director, Clinical Trial Disclosure & Transparency
Jazz Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee The sponsor can review trial results communications prior to public release and can embargo such communications for a period of at least 60 days from the time submitted to sponsor for review. If requested by sponsor, the PI will withhold publication for up to an additional 30 days. Furthermore, the first publication of study results must be a joint publication of all study sites unless a joint manuscript has not been submitted for publication within 12 months of completion of the study.
- Publication restrictions are in place
Restriction type: OTHER