A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate the Safety and Efficacy of Pitolisant in Patients With Prader-Willi Syndrome, Followed by an Open Label Extension

• Is able to provide voluntary, written informed consent (patient or parent\[s\]/legal guardian\[s\]) and, where applicable, voluntary, written assent (patient, as appropriate).

• Has a diagnosis of PWS confirmed by genetic testing and/or patient medical records. Genetic testing will be provided by the Sponsor, if not confirmed based on the review of the patient's medical records.

• Male or female patients ages 6 to 65 years at the time of enrollment.

• Demonstrates adequate sleep duration via patient sleep diary during Screening, defined as at least 8 hours of sleep per night for patients ages 6 to \<12 years, at least 7 hours for patients ages 12 to \<18 years, or at least 6 hours for patients ages ≥18 years, based on the mean number of hours from up to 14 nights (at least 7 nights must be recorded for evaluation).

• Has EDS as determined by Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD) (parent/caregiver version) score of ≥12.

• If taking hormone treatments (including growth hormone, testosterone, and estrogen supplements) and/or allowed chronic concomitant medication or supplements, patient must be on a stable dose of these medications for 3 months prior to randomization and for the duration of the Double-Blind Treatment Phase of the study; a 10% variability in hormone dose is allowed.

• If taking a wake-promoting treatment that could affect EDS (including stimulants, modafinil, and armodafinil), must be on a stable dose for at least 28 days prior to Screening and remain on a stable dose during the Double-Blind Treatment Phase of the study (dose adjustments will be permitted in the OLE Phase) or agree to wash out of treatment for 5 half-lives or 14 days, whichever is longer.

• If taking a chronically administered sedating medication for management of behavioral manifestations (e.g., hypnotics, benzodiazepines, antipsychotics, alpha agonists, anticholinergics, and antidepressants) must be on a stable dose for at least 28 days prior to Screening and remain on a stable dose during the Double-Blind Treatment Phase of the study (dose adjustments will be permitted in the OLE Phase) or agree to wash out of treatment for 5 half-lives or 14 days, whichever is longer.

• If using cannabidiol and/or tetrahydrocannabinol, patient must be on a stable dose for 28 days prior to randomization and agree to continue the stable dose for the duration of the Double-Blind Treatment Phase of the study (dose adjustments will be permitted in the OLE Phase).

⁃ If taking oxytocin or carbetocin, patient must be on a stable dose during the 28 days prior to randomization and agree to continue the stable dose for the duration of the Double-Blind Treatment Phase of the study (dose adjustments will be permitted in the OLE Phase) or agree to wash out of treatment for 5 half-lives or 14 days, whichever is longer.

⁃ A patient who is a female of child-bearing potential (FCBP) must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at the Baseline Visit and agree to remain abstinent or use an effective method of nonhormonal contraception to prevent pregnancy for the duration of the study and for 21 days after final dose of study drug.

⁃ Has a consistent caregiver (preferably the same person throughout the Double-Blind Treatment Phase of the study) who is willing and able to complete the required assessments.

⁃ In the opinion of the Investigator, patient/parent(s)/legal guardian(s) is capable of understanding and complying with the requirements of the protocol and administration of oral study drug.