{"doi":"10.3233/jpd-212714","title":"Safety, Pharmacokinetics, and Pharmacodynamics of Oral Venglustat in Patients with Parkinson’s Disease and a GBA Mutation: Results from Part 1 of the Randomized, Double-Blinded, Placebo-Controlled MOVES-PD Trial","abstract":"BACKGROUND: Glucocerebrosidase gene (GBA) mutations influence risk and prognosis of Parkinson's disease (PD), possibly through accumulation of glycosphingolipids, including glucosylceramide (GL-1). Venglustat is a novel, brain penetrant glucosylceramide synthase inhibitor. OBJECTIVE: Evaluate venglustat pharmacology, safety, and tolerability in patients with PD and GBA mutations (GBA-PD). METHODS: Part 1 of the phase 2 MOVES-PD trial (NCT02906020) was a randomized, double-blinded, placebo-controlled, dose-escalation study performed in six countries. Eligible participants included Japanese and non-Japanese patients aged 18-80 years with PD diagnosis and heterozygous GBA mutation. Participants were randomized to three doses of once-daily oral venglustat or placebo and were followed up to 36 weeks (Japanese participants: 52 weeks). Primary endpoint was venglustat safety and tolerability versus placebo. Secondary and exploratory endpoints included venglustat pharmacokinetics and pharmacodynamics. RESULTS: Participants (N = 29) received venglustat (Japanese, n = 9; non-Japanese, n = 13) or placebo (n = 3; n = 4). Eight (89%) Japanese and 12 (92%) non-Japanese venglustat-treated participants experienced at least one adverse event (AE) versus two (67%) and four (100%) participants from the respective placebo groups. Most AEs were mild or moderate; no serious AEs or deaths occurred. Two venglustat-treated non-Japanese participants discontinued due to AEs (confusional state and panic attack). Over 4 weeks, venglustat exposure in plasma and cerebrospinal fluid (CSF) increased, and GL-1 levels in plasma and CSF decreased, both in a dose-dependent manner. At the highest dose, CSF GL-1 decreased by 72.0% in Japanese and 74.3% in non-Japanese participants. CONCLUSION: Venglustat showed favorable safety and tolerability in MOVES-PD Part 1 and target engagement was achieved in CSF.","journal":"Journal of Parkinson s Disease","year":2021,"id":154971,"datarank":1.7041402137460908,"base_score":4.127134385045092,"endowment":4.127134385045092,"self_citation_contribution":0.6190701577567639,"citation_network_contribution":1.085070055989327,"self_endowment_contribution":0.6190701577567639,"citer_contribution":1.085070055989327,"corpus_percentile":null,"corpus_rank":null,"citation_count":61,"citer_count":49,"citers_with_citation_signal":40,"citers_with_endowment":40,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9573,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02906020"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":657613,"name":"on behalf of the MOVES-PD Investigators","orcid":null,"position":1,"is_corresponding":false},{"id":656539,"name":"Hidemoto Saiki","orcid":"0000-0003-0227-0103","position":2,"is_corresponding":false},{"id":656540,"name":"Taku Hatano","orcid":"0000-0002-6808-0444","position":3,"is_corresponding":false},{"id":249059,"name":"Thomas Gasser","orcid":"0000-0002-1069-1146","position":4,"is_corresponding":false},{"id":309338,"name":"Stuart Isaacson","orcid":"0000-0002-9914-5706","position":5,"is_corresponding":false},{"id":657614,"name":"Sebastiaan J.M. Gaemers","orcid":null,"position":6,"is_corresponding":false},{"id":657615,"name":"Pascal Minini","orcid":null,"position":7,"is_corresponding":false},{"id":657616,"name":"Stéphane Saubadu","orcid":null,"position":8,"is_corresponding":false},{"id":426130,"name":"Jyoti Sharma","orcid":"0000-0002-5666-8996","position":9,"is_corresponding":false},{"id":657617,"name":"Samantha Walbillic","orcid":null,"position":10,"is_corresponding":false},{"id":279481,"name":"Roy N. Alcalay","orcid":"0000-0002-5717-4875","position":11,"is_corresponding":false},{"id":270886,"name":"Gary Cutter","orcid":"0000-0002-8455-980X","position":12,"is_corresponding":false},{"id":17418,"name":"Nobutaka Hattori","orcid":"0000-0002-2034-2556","position":13,"is_corresponding":false},{"id":84353,"name":"Günter U. Höglinger","orcid":"0000-0001-7587-6187","position":14,"is_corresponding":false},{"id":80317,"name":"Kenneth Marek","orcid":"0000-0002-4197-5627","position":15,"is_corresponding":false},{"id":656541,"name":"Anthony H.V. Schapira","orcid":"0000-0002-3018-3966","position":16,"is_corresponding":false},{"id":271547,"name":"Clemens R. Scherzer","orcid":"0000-0002-0567-9193","position":17,"is_corresponding":false},{"id":246441,"name":"Tanya Simuni","orcid":"0000-0002-2347-1644","position":18,"is_corresponding":false},{"id":388724,"name":"Nir Giladi","orcid":"0000-0003-1482-8522","position":19,"is_corresponding":false},{"id":279483,"name":"S. Pablo Sardi","orcid":"0000-0001-9805-3677","position":20,"is_corresponding":false},{"id":656542,"name":"Tanya Fischer","orcid":"0000-0003-3204-5660","position":21,"is_corresponding":false},{"id":656538,"name":"Michel Peterschmitt","orcid":"0000-0003-4686-0412","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-18T23:43:59.154159Z","pmid":"34897099","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}