An international, randomized, placebo‐controlled, phase 2b clinical trial of intepirdine for dementia with Lewy bodies (HEADWAY‐DLB)

Abstract

Introduction A phase 2b clinical trial, HEADWAY‐DLB, was performed to assess treatment with intepirdine, a serotonin receptor antagonist, in patients with dementia with Lewy bodies (DLB). Methods HEADWAY‐DLB was a multinational, double‐blind, randomized, placebo‐controlled study. Two hundred sixty‐nine DLB patients were randomized to receive placebo, 70 mg/day intepirdine, or 35 mg/day intepirdine over 24 weeks. The primary endpoint was change from baseline to week 24 on the Unified Parkinson's Disease Rating Scale–Part III (UPDRS‐III). Results Both intepirdine groups did not demonstrate significant benefits over placebo at 24 weeks on the UPDRS‐III (35 mg/day: P = .1580, 70 mg/day: P = .6069). All other endpoints were not significant. Intepirdine was well tolerated, with a slightly higher incidence of gastrointestinal adverse events observed in the intepirdine groups versus placebo. Discussion Intepirdine treatment did not lead to improvements over placebo in patients with DLB. As one of the largest DLB studies to date, HEADWAY‐DLB demonstrates that international trials for DLB are feasible within a reasonable timeframe.

Effect of masupirdine (SUVN‐502) on cognition in patients with moderate Alzheimer's disease: A randomized, double‐blind, phase 2, proof‐of‐concept study

“…22 Landipirdine and intepirdine were evaluated for their potential benefits in Parkinson's disease dementia and dementia with Lewy bodies, respectively. 23,24 No benefits were observed in either disease population. Overall, inconsistent treatment effects were observed on cognition with 5-HT 6 receptor antagonists when tested as a standalone treatment or as an adjunct to cholinesterase inhibitors.…”

“…Another 5‐HT 6 receptor antagonist, PF‐05212377 (SAM‐760), was evaluated for its potential benefits on cognition in patients with mild to moderate AD dementia and neuropsychiatric symptoms but its study was terminated after an interim analysis showed no benefits on cognition or neuropsychiatric symptoms 22 . Landipirdine and intepirdine were evaluated for their potential benefits in Parkinson's disease dementia and dementia with Lewy bodies, respectively 23,24 . No benefits were observed in either disease population.…”

Clinical outcome measures in dementia with Lewy bodies trials: critique and recommendations

“…The UPDRS is responsive to therapeutic interventions and is the reference scale for regulatory agencies [ 156 , 157 ]. Moreover, it has been used as a primary outcome in DLB trials targeting motor function [ 99 , 158 ]. The MDS-UPDRS is a newer version that differs from the UPDRS especially in the evaluation of non-motor aspects of PD [ 27 ].…”

Advances in dementia with Lewy bodies

“…66 In addition to these active disease-modifying trials, numerous trials of symptomatic therapies with diverse mechanisms of action are completed or underway (Table 4). Unfortunately, many of these studies, including the recently published HEADWAY-DLB trial, 67 showed no clear efficacy, although peer-reviewed publications for several studies remain lacking. While disappointing, these trials demonstrate that clinical trials in DLB are feasible, including in international settings.…”

“…While disappointing, these trials demonstrate that clinical trials in DLB are feasible, including in international settings. 67 Recently, the AscenD-LB study (NCT04001517) met its primary objective of improving cognition in individuals with DLB and a phase III study is planned. 68…”