Journal article
Huntington's Disease Progression: A Population Modeling Approach to Characterization Using Clinical Rating Scales
Journal of clinical pharmacology, Vol.60(8), pp.1051-1060
08/2020
DOI: 10.1002/jcph.1598
PMID: 32416008
Abstract
Development of effective therapeutics that slow Huntington's disease progression is a research priority that requires an understanding of natural disease progression. We applied a population‐modeling approach to describe the progression of 2 routinely used rating scales — the total motor score and the total functional capacity score. Models were fitted to data from research participants aged ≥ 18 years with Huntington's disease stage I or II at study entry (total functional capacity score ≥ 7), from a controlled clinical trial (CARE‐HD) and 2 observational studies (COHORT and Registry). A logistic model without shape factors was selected as the base model based on placebo data from CARE‐HD and validated using data from the CARE‐HD active‐treatment arms. Albeit with a smaller progression rate constant than was found in CARE‐HD, the proposed models provided reasonable predictions for both rating scales in the pooled data from COHORT and Registry and were considered suitable for use in clinical trial simulations. Results also showed that disease burden score (a product of age and expanded CAG length) is a significant covariate on both the progression rate constant and the baseline score in the total motor score model. These findings suggest that total motor score and total functional capacity progress fastest near their half‐maximal score, implying that the efficiency of clinical trials evaluating disease‐modifying therapeutics for Huntington's disease could be enhanced by enrolling patients with faster disease progression or evaluating treatment effect near their half‐maximal score, provided that the evaluated therapy is expected to be efficacious at this disease stage.
Details
- Title: Subtitle
- Huntington's Disease Progression: A Population Modeling Approach to Characterization Using Clinical Rating Scales
- Creators
- Wan Sun - Food and Drug AdministrationDi Zhou - Food and Drug AdministrationJohn H Warner - CHDI Management/CHDI FoundationDouglas R Langbehn - University of IowaGuenther Hochhaus - University of FloridaYaning Wang - Food and Drug Administration
- Resource Type
- Journal article
- Publication Details
- Journal of clinical pharmacology, Vol.60(8), pp.1051-1060
- DOI
- 10.1002/jcph.1598
- PMID
- 32416008
- ISSN
- 0091-2700
- eISSN
- 1552-4604
- Number of pages
- 10
- Grant note
- CHDI Foundation
- Language
- English
- Date published
- 08/2020
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984066382002771
Metrics
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