Study Name	Groups Studied and Intervention	Results and Findings	Conclusions
P05-03	22 participants were randomly assigned to Pitolisant and placebo regimens, each of which lasted seven days. Primary outcomes were measured using the Epworth Sleepiness Scale (ESS).	Participants saw a notable reduction in ESS scores from a baseline of 17.55±3.89 to 11.81±6.11. Pitolisant treatment represents a 4.86±5.12 reduction in ESS compared to placebo, and a 5.85±5.51 reduction relative to baseline.	Pitolisant demonstrates no statistically significant benefit over baseline.
P06-06	26 participants were administered varying doses of Pitolisant for a maximum of nine months to evaluate efficacy of escalated doses. Primary outcomes were measured using the ESS.	Participants received either 10, 20, or 40 mg daily doses for a maximum of nine months and were evaluated at one-, three-, and nine-month intervals. These regimens resulted in ESS score reductions of 4.8, 5.3, and 6.9 points, respectively.	The efficacy of Pitolisant is dose-dependent, suggesting 40 mg would demonstrate most therapeutic value.
Harmony I	95 participants from 32 centers across Europe were randomly assigned to either Pitolisant (n=32), Modafinil (n=33), or placebo (n=30) for eight weeks, to evaluate efficacy of Pitolisant relative to standard Modafinil therapy. Primary outcomes were measured using the ESS.	Treatment schedule over eight weeks: three weeks of flexible dosing (10, 20, or 40 mg/day of pitolisant; 100, 200, or 400 mg/day of modafinil) followed by five weeks of a steady dose of either Pitolisant or Modafinil. By the end of eight weeks, mean ESS score reductions were -3.4±4.2 for placebo, -5.8±6.2 for Pitolisant, and -6.9±6.2 for Modafinil.	No demonstration of Pitolisant’s superiority relative to Modafinil.
Harmony Ibis	165 participants were divided randomly into Pitolisant (n=67), Modafinil (n=65), or placebo (n=33) groups to evaluate efficacy of Pitolisant relative to standard Modafinil therapy. Primary outcomes were measured using the ESS.	Flexible dosing for first three weeks of treatment: 10 or 20 mg daily of Pitolisant; or 100, 200, or 400 mg daily of Modafinil. Flexible treatment was followed by five weeks of stable dosing. The mean ESS score reductions follow the eight-week regimen: -3.6±5.6 for placebo, -4.6±4.6 for Pitolisant, and -7.8±5.9 for Modafinil). Difference in mean ESS scores of only -1.94 (95% CI of -4.005 to -0.07; p=0.06) between Pitolisant and placebo, thus failing to meet efficacy criterion of a difference of at least three ESS points. Non-inferiority of Pitolisant relative to Modafinil could not be established, as data demonstrate a difference of -2.75 (95% CI -4.48 to -1.02) which failed to meet the pre-established cutoff of three points	When subjected to an unplanned superiority analysis of Modafinil relative to Pitolisant, the Modafinil group demonstrated a much greater mean ESS score reduction. Thus, Pitolisant failed to demonstrate superiority to both placebo and Modafinil
Harmony III	102 participants with narcolepsy, with or without cataplexy, were enrolled in an open-label trial, 68 of which completed a twelve-month treatment period. Primary endpoint was incidence of Treatment-Emergent Adverse Effects (TEAE) at twelve months, while secondary endpoints were measured using the (ESS).	Participants started with one week of 5 mg Pitolisant daily, followed by a week of 10 mg daily, followed by a week of 20 mg, subject to safety and tolerability. After a month, the investigator could titrate the dose to 40mg if lower doses were not deemed efficacious. Commonly-reported TEAEs rwere headache (11.8%), insomnia (8.8%), weight gain (7.8%), anxiety (6.9%), depressed mood (4.9%), and nausea (4.9%). Also reported were seven instances of severe adverse effects, all of which were deemed unrelated to Pitolisant therapy. Nearly 67% of those who finished the treatment regimen were deemed responders with either an end-treatment ESS ≤ 10 or a reduction in ESS ≥ 3, while the remaining 33% demonstrated a normalized ESS (i.e. ESS ≤ 10).	The vast majority of TEAEs reported while on Pitolisant therapy were mild to moderate; only 6.55% were severe and related to the study drug. In terms of secondary goals, Pitolisant demonstrated a high response rate at therapeutic dosages.
Harmony CTP (P11-05)	145 narcoleptic participants were divided into Pitolisant and placebo groups, each of which was given a seven-week regimen consisting of three weeks of flexible Pitolisant dosing (5, 10, or 20 mg daily) followed by four weeks of stable dosing (5, 10, 20, or 40 mg daily). This study sought to evaluate the effect of Pitolisant versus placebo on reducing cataplectic episodes in narcoleptic patients, measured as the number of episodes per week. Secondary objectives evaluated the effect of Pitolisant on EDS, measured using the ESS.	When measured relative to the frequency of cataplexy during a two-week baseline period, the stable dosing period showed a reduction in episodes per week for the Pitolisant group from 9.15 to 3.28, and the placebo group from 7.31 to 6.79. At the study’s conclusion, the percentage of participants demonstrating a high frequency of cataplectic episodes (defined as >15 episodes/week) was significantly higher in the placebo group (23.5%; 95% CI of 12 to 51) relative to the Pitolisant group (5.6%; 95% CI of 3 to 54). Harmony CTP demonstrated significant reduction in mean ESS scores relative to the placebo group. The placebo group showed a mean ESS score change of -1.9±4.3 (p<0.001) relative to baseline values, while the Pitolisant group exhibited a change of -5.4±4.3 (p<0.001).	There was a statistically significant reduction in cataplectic episodes in the Pitolisant group relative to placebo. Additionally, relative to placebo, Pitolisant showed a statistically significant reduction in overall EDS.