Objective: To assess retention and safety in the ongoing TOPAZ trial, NCT03924414

Background: People with NDP face a four-fold increased fracture risk, yet preventive treatment is underutilized. TOPAZ is a fully home-based, double-blind, placebo-controlled, randomized clinical trial assessing the efficacy and safety of zoledronate, an FDA-approved bisphosphonate. The home-based design aims to improve accessibility to clinical trials, including persons with advanced disease.

Method: Persons aged > 60 are referred to the study website from multiple sources, including Parkinson Study Group centers and community outreach. All study procedures, including consent and movement disorder expert eligibility determination (medical record review, telemedicine) are conducted remotely. Additional eligibility assessments, randomization and administration of zoledronate or placebo are conducted by research nurses in participants’ homes. Safety monitoring includes post-infusion adverse event (AE) assessments and long-term follow-up. Fractures are ascertained every 4 months for up to 5 years by email or telephone and adjudicated by expert review. Here we report safety and retention data through 2/19/25 by diagnosis, disease severity, and cognitive status.

Results: As of  2/19/25, 5,046 persons consented, 3,811 were eligible, 2,569 were randomized [Table1]. Parkinson’s disease (PD) was the most common diagnosis (90%), then NDP not specified (4%) and progressive supranuclear palsy (PSP) (2%).  More men were randomized (66%). Mean age at randomization was 71.2 years (range 60-93). Among 178  SAEs,  death not attributed to study drug was most common (n=170). AEs were reported by 134 people. Among acute AEs (n =125) those associated with a well described post infusion reaction were most common [Figure1]. Nonacute AEs led to study withdrawal in 1.3%. Follow-up to determine fracture outcomes (retention) is 92.4% overall (women 90.6%, men 96.1%).  Retention is high across all diagnoses (range: 86%-100%), in mild and severe disease (>96% in all), and in those with MCI or dementia (99%) [Tables 2,3].

Conclusion: The fully remote design of TOPAZ facilitates participation among those at greatest risk of fractures. Safety is good, and retention is high in those with cognitive impairment, in those with reduced mobility and in all diagnostic groups.  

Table 1

Table 2

Table 3

Figure 1

Figure 2

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MDS Abstracts - https://www.mdsabstracts.org/abstract/retention-safety-in-a-home-based-fracture-prevention-trial-of-zoledronate-vs-placebo-topaz-in-persons-with-neurodegenerative-parkinsonism-ndp/