OBJECTIVES: The caregiver-completed Hyperphagia Questionnaire (HQ) is commonly used to assess food-seeking behaviours in Prader-Willi syndrome (PWS). A modified version, the HQ for Clinical Trials (HQ-CT), was developed and adapted for use in multinational PWS clinical trials. METHODS: The 13-item HQ was reviewed and modified based on industry and regulatory standards. The preliminary HQ-CT was included in a phase 2 trial; data analysis informed psychometric evaluation and optimal scoring. Further refinements were made following Food and Drug Administration (FDA), clinical reviews, and interviews with PWS caregivers in the United States (US). The final 9-item HQ-CT was culturally adapted to 10 European languages using industry standards for forward-back translation, followed by cognitive debriefing interviews (CDIs) with PWS caregivers in target countries to assess content validity. RESULTS: Review of the 13-item HQ removed three items to limit content to observable behaviours that could change after treatment. Analysis of trial data provided support for an HQ-CT composite score (e.g., alpha coefficients ≥ 0.85), as well as the measure’s validity and responsiveness. One item was removed based on FDA recommendation, yielding a 9-item HQ-CT CONCLUSIONS: The development of the HQ-CT and its adaptation to 10 European languages, with input from 56 caregivers, has produced a valuable instrument for assessing food-seeking behaviours in PWS clinical trials in the US and Europe.