Granulin Mutation
Conditions
Keywords
Histone deacetylase inhibitor, Frontotemporal dementia, Granulin
Brief summary
The purposes of this study are to investigate the safety, tolerability, and pharmacodynamics of FRM-0334 in subjects with prodromal to moderate frontotemporal dementia with granulin mutation.
Interventions
DRUGFRM-0334
DRUGPlacebo
Sponsors
FORUM Pharmaceuticals Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male or female ages aged ≥21 and ≤75 years * Genotyped positive for a FTD-GRN mutation, and aware of it * Prodromal to moderate FTD-GRN * Resides in a stable living situation, living at home, senior residential setting, or an institutional setting without the need for continuous (ie, 24-hour) nursing care * Proficiency (oral and written) in the language in which study-related documents, including the ICF and standardized tests, will be administered * Able to swallow capsules * Be in good general health, willing and able to comply with the protocol requirements, and expected to complete the study as designed (in the judgment of the investigator)
Exclusion criteria
* Clinically significant abnormalities on physical examination, medical history, ECG, vital signs, laboratory values, or unstable medical or psychiatric illness * Females who are pregnant, breastfeeding, or planning to become pregnant during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the safety and tolerability of FRM-0334 | Baseline to Day 28 or Early Termination | * Number and percentage of subjects with AEs * Number and percentage of subjects with SAEs * Number and percentage of subjects who discontinue due to AEs * Number and percentage of subject deaths |
| Assess the pharmacodynamic (PD) effects of FRM-0334 on the change from baseline in plasma concentrations of progranulin (PGRN) after 28 days | Baseline to Day 28 or Early Termination | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess the pharmacodynamic effects of FRM-0334 on the change from baseline in cerebrospinal fluid (CSF) concentrations of PGRN after 28 days | Baseline and Day 28 | Change in CSF progranulin concentration from baseline |
| Characterize the plasma concentrations of FRM-0334 and metabolites following once daily dosing for 28 days | Day 1 to Day 28 or Early Termination | Cmax, Ctrough, tmax, t1/2, λz, AUC(0-τ), CL/F, Cav in plasma |
| Characterize the CSF concentrations of FRM-0334 and metabolites following once daily dosing for 28 days | Day 1 to Day 28 or Early Termination | Cmax, Ctrough, tmax, t1/2, AUC0-τ, CL/F, Cav in CSF |
Countries
Belgium, France, Italy, Netherlands, United Kingdom, United States
Outcome results
None listed