A proof-of-concept study of pitolisant for excessive daytime sleepiness in patients with Prader-Willi syndrome
Abstract
STUDY OBJECTIVES: The majority of patients with Prader-Willi syndrome experience excessive daytime sleepiness (EDS). This study evaluated the effects of pitolisant, a histamine 3 (H3)-receptor antagonist/inverse agonist that promotes wakefulness, in patients with Prader-Willi syndrome and EDS.
METHODS: In this phase 2, randomized, double-blind, placebo-controlled, proof-of-concept study, patients ages 6-65 years with a confirmed diagnosis of Prader-Willi syndrome with EDS were randomized 1:1:1 to receive lower-dose pitolisant (children/adolescents/adults, 8.9/13.35/17.8 mg), higher-dose pitolisant (children/adolescents/adults, 17.8/26.7/35.6 mg), or matching placebo for 11 weeks (3-week titration/8-week maintenance). The primary endpoint was change from baseline to week 11 in Epworth Sleepiness Scale for Children and Adolescents (parent/caregiver version) score. Other measures included the Caregiver Global Impression of Severity for EDS, Aberrant Behavior Checklist-Community, second edition, and Hyperphagia Questionnaire for Clinical Trials.
RESULTS: Of 65 patients randomized and treated, 59 (90.8%) completed the double-blind phase. Least-squares (LS) mean improvement from baseline to week 11 in Epworth Sleepiness Scale for Children and Adolescents score was greater for higher-dose pitolisant (-5.0) vs placebo (-3.9; LS mean [standard error] difference, -1.1 [1.52]), but not for lower-dose pitolisant (-3.5) vs placebo (LS mean [standard error] difference, 0.5 [1.6]). The…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 65 participants or records.
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