Study to Assess the Safety, Tolerability, and Pharmacodynamic (PD) Effects of FRM-0334 in Subjects With Prodromal to Moderate Frontotemporal Dementia With Granulin Mutation

Overview

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.

Full Title of Study: “A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalating, Phase 2a Safety, Tolerability, and Pharmacodynamic Study of Two Doses of an Histone Deacetylase Inhibitor (FRM-0334) in Subjects With Prodromal to Moderate Frontotemporal Dementia With Granulin Mutation”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: August 2016

Interventions

  • Drug: FRM-0334
  • Drug: Placebo

Arms, Groups and Cohorts

  • Experimental: FRM-0334; Arm 1
    • low dose, Capsule, Once Daily, Day 1 through Day 28
  • Experimental: FRM-0334; Arm 2
    • high dose, Capsule, Once Daily, Day 1 through Day 28
  • Placebo Comparator: Placebo Comparator; Arm 3
    • Placebo, Capsule, Once Daily, Day 1 through Day 28

Clinical Trial Outcome Measures

Primary Measures

  • Evaluate the safety and tolerability of FRM-0334
    • Time Frame: 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
    • Time Frame: Baseline to Day 28 or Early Termination

Secondary Measures

  • Assess the pharmacodynamic effects of FRM-0334 on the change from baseline in cerebrospinal fluid (CSF) concentrations of PGRN after 28 days
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: Day 1 to Day 28 or Early Termination
    • Cmax, Ctrough, tmax, t1/2, AUC0-τ, CL/F, Cav in CSF

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 21 Years

Maximum Age: 75 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • FORUM Pharmaceuticals Inc
  • Provider of Information About this Clinical Study
    • Sponsor

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