A Multicenter Study of the Efficacy and Safety of JZP-258 in the Treatment of Idiopathic Hypersomnia (IH) With an Open-label Safety Extension

The ESS is a 8-item self reported questionnaire intended to measure daytime sleepiness. In this test, participants answer questions with regard to the level of sleepiness they experienced over approximately the 7 days prior to the assessment while performing eight common, non-stimulating activities. The ESS total score range is 1 to 24. Each activity is rated on a 4-point scale ranging from a minimum of would never doze to a maximum of a high chance of dozing. Thus, the ESS scale range is as follows: 0=would never doze, 1=slight chance of dozing, 2=moderate chance of dozing, 3=high chance of dozing; 0 indicates a better outcome, and 3 indicates a worse outcome. A positive mean change value indicates an increase in score from the end of the stable dose period and worsened daytime sleepiness. A higher ESS score (above 10) reflects a greater average sleep propensity in daily life (ASP) , or daytime sleepiness.

Time frame: Change from the end of the Stable Dose Period to the end of the Double-blind Randomized Withdrawal Period (DBRW) (2 Weeks)

Population: The Modified Intent to Treat (mITT) analysis set included all participants who were randomized to JZP258 or placebo, who received at least 1 dose of study drug during the DBRW and have had at least one set of post randomization assessments for ESS or IHSS, or a PGIc value at the end of the DBRW.

The FOSQ-10 is a short version of the original FOSQ-30 instrument, which is a disease specific quality of life questionnaire to determine functional status in adults. Measures are designed to assess the impact of disorders of excessive sleepiness on multiple activities of everyday living and the extent to which these activities are improved by effective treatment. The questionnaire has a 4-point Likert response format (e.g., 1= extreme difficulty, 2= moderate difficulty, 3=a little difficulty, and 4 =no difficulty). FOSQ-10 total score is calculated by first taking the mean of the items for each subscale with more than 1 item completed and then taking the mean across the non-missing 5 subscales (General Productivity, Activity Level, Vigilance, Social Outcomes, Intimacy and Sexual Relationship) multiplied by 5. The score ranges from a minimum of 5 points to a maximum of 20 points, with higher scores indicating better functional status.

Time frame: Change from the end of the Stable Dose Period to the end of the DBRW Period (2 Weeks)

Population: The Modified Intent to Treat (mITT) analysis set included all participants who were randomized to JZP258 or placebo, who received at least 1 dose of study drug during the DBRW and have had at least one set of post randomization assessments for ESS or IHSS, or a PGIc value at the end of the DBRW. JZP-258 overall number was 54 and placebo group overall number was 56 as fewer participants were available for this particular assessment.

The IHSS is a 14-item self-reported questionnaire assessing the severity of IH symptoms of excessive sleepiness, prolonged sleep duration, cognitive impairment and sleep inertia. Total scores can range from 0 to 50, with higher scores indicating a greater severity or frequency of symptoms.

Time frame: Change from the end of the Stable Dose Period to the end of the DBRW Period (2 Weeks)

Population: The Modified Intent to Treat (mITT) analysis set included all participants who were randomized to JZP258 or placebo, who received at least 1 dose of study drug during the DBRW and have had at least one set of post randomization assessments for ESS or IHSS, or a PGIc value at the end of the DBRW.

The CGIc scale is a 7-point Likert-type scale that rates the Investigator's impression of any change in the severity of the participant's condition at a specified time point. The participant was rated on a 7-point scale ranging from a minimum of Very much improved to a maximum of Very much worse. The CGIc scale consists of the following ratings: 1-Very Much improved, 2-Much improved, 3-Minimally improved, 4-No change, 5-Minimally worse, 6-Much worse, 7-Very much worse; a rating of 1 indicates a better outcome, and a rating of 7 indicates a worse outcome. Worsened condition was defined as a CGIc rating of 5, 6, or 7.

Time frame: At the end of the DBRW Period (2 Weeks)

Population: The Modified Intent to Treat (mITT) analysis set included all participants who were randomized to JZP258 or placebo, who received at least 1 dose of study drug during the DBRW and have had at least one set of post randomization assessments for ESS or IHSS, or a PGIc value at the end of the DBRW.

The Patient Global Impression - Change (PGIc) scale was completed by the participant. The PGI-C scale rated the participant's condition at a specified time point on a 7-point scale ranging from a minimum of Very much improved to a maximum of Very much worse. The PGIc scale consists of the following ratings: 1-Very Much improved, 2-Much improved, 3-Minimally improved, 4-No change, 5-Minimally worse, 6-Much worse, 7-Very much worse; a rating of 1 indicates a better outcome, and a rating of 7 indicates a worse outcome. Worsened condition was defined as a PGIc rating of 5, 6, or 7.

Time frame: At the end of the DBRW Period (2 Weeks)

Population: The Modified Intent to Treat (mITT) analysis set included all participants who were randomized to JZP258 or placebo, who received at least 1 dose of study drug during the DBRW and have had at least one set of post randomization assessments for ESS or IHSS, or a PGIc value at the end of the DBRW.