Evaluation of Tolfenamic Acid in Individuals With PSP at 12-Weeks

NCT04253132 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: NT 101-201
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a 12-week study of oral tolfenamic acid vs. placebo in Progressive Supranuclear Palsy (PSP)

Conditions

Progressive Supranuclear Palsy

Outcome Measures

Primary Outcomes (1)

• Safety and tolerance of tolfenamic acid in individuals with PSP

  Safety measures include: number of AEs, ECG changes, nasal examination and clinical laboratory tests

  12-weeks

Secondary Outcomes (7)

• CSF biomarker change from baseline

  12-weeks

• Pharmacodynamic parameter of amyloid beta peptide

  12-weeks

• Pharmacodynamic parameter of total tau

  12-weeks

• Pharmacodynamic parameter of phosphorylated tau

  12-weeks

• Pharmacodynamic parameter of NFL

  12-weeks

Other Outcomes (10)

• Clinical global Impression of Change

  12-weeks

• Progressive Supranuclear Pallsy Rating Scale (PSPRS)

  12-weeks

• Schwab and England Activities of Daily Living Scale (SEADL)

  12-weeks

Study Arms (6)

50 mg daily oral dose

ACTIVE COMPARATOR

50 mg daily, oral dose of tolfenamic acid

Drug: Tolfenamic Acid

300 mg daily oral dose

ACTIVE COMPARATOR

300 mg daily, oral dose of tolfenamic acid

Drug: Tolfenamic Acid

600 mg daily oral dose

ACTIVE COMPARATOR

50 mg daily, oral dose of tolfenamic acid

Drug: Tolfenamic Acid

Placebo control - 50 mg daily oral dose

PLACEBO COMPARATOR

50 mg daily oral placebo control

Drug: Placebos

Placebo control - 300 mg daily oral dose

PLACEBO COMPARATOR

300 mg daily oral placebo control

Drug: Placebos

Placebo control - 600 mg daily oral dose

PLACEBO COMPARATOR

600 mg daily oral placebo control

Drug: Placebos

Interventions

Tolfenamic Acid DRUG

Tolfenamic acid is an NSAID closely resembling mefenamic and flufenamic acid.

Also known as: NT101

300 mg daily oral dose; 50 mg daily oral dose; 600 mg daily oral dose

Placebos DRUG

oral placebo

Also known as: placebo

Placebo control - 300 mg daily oral dose; Placebo control - 50 mg daily oral dose; Placebo control - 600 mg daily oral dose

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects may be included in the study only if they meet all of the following criteria:
• Probable or possible progressive supranuclear palsy defined as:
• At least a 12-month history of postural instability or falls during the first 3 years that symptoms are present; and
• At screening (Visit 1), a decreased downward saccade velocity defined as observable eye movement (deviation from the "main sequence" linear relationship between saccade amplitude and saccade velocity), or supranuclear ophthalmoplegia defined as 50% reduction in upward gaze or 30% reduction in downward gaze; and
• Age at symptom onset of 40 to 85 years by history; and
• An akinetic-rigid syndrome with prominent axial rigidity.
• Aged 41 to 85 years at the time of screening (Visit 1).
• Judged by investigator to be able to comply with neuropsychological evaluation at baseline and throughout the study.
• Must have reliable caregiver accompany subject to all study visits. Caregiver must read, understand, and speak local language fluently to ensure comprehension of informed consent form and informant-based assessments of subject. Caregiver must also have frequent contact with subject (at least 3 hours per week at one time or at different times) and be willing to monitor study medication compliance and the subject's health and concomitant medications throughout the study.
• Modified Hachinski score ≤ 3. This modified Hachinski will not include the focal neurological signs, symptoms or pseuodobulbar affect questions, given the prominence of all 3 in PSP.
• Score ≥ 15 on the Mini-Mental State Examination (MMSE) at screening (Visit 1).
• Written informed consent provided by subject (or legally-appointed representative, as appropriate) and caregiver (if not the legally-appointed representative) who are both fluent local language speakers.
• Subject resides outside a skilled nursing facility or dementia care facility at the time of screening (Visit 1), and admission to such a facility is not planned. Residence in an assisted living facility is allowed.
• If the subject is receiving levodopa/carbidopa, levodopa/benserazide, a dopamine agonist, catechol-o- methyltransferase (COMT) inhibitor, or other Parkinson's medication with the exception of Azilect (rasagiline), the dose must have been stable for at least 60 days prior to the screening visit (Visit 1) and must remain stable for the duration of the study. No such medication can be initiated during the study. Subjects receiving rasagiline or CoQ10 must be on a stable dose for at least 90 days prior to the screening visit (Visit 1).
• Able to tolerate the MRI scan during screening with either no sedation or low dose lorazepam..

You may not qualify if:

• Subjects will be excluded from the study for any of the following reasons:
• Insufficient fluency in local language to complete neuropsychological and functional assessments.
• A diagnosis of Amyotrophic Lateral Sclerosis (ALS) or other motor neuron disease.
• Any of the following:
• Cerebellar ataxia,
• Choreoathetosis,
• Early, symptomatic autonomic dysfunction, or
• Tremor while at rest.
• Presence of other significant neurological or psychiatric disorders including (but not limited to) Alzheimer's disease; dementia with Lewy bodies; prion disease; Parkinson's disease (which has not subsequently been revised to PSP), any psychotic disorder; severe bipolar or unipolar depression; seizure disorder; tumor or other space-occupying lesion; or history of stroke or head injury with loss of consciousness for at least 15 minutes within the past 20 years.
• Within 4 weeks of screening (Visit 1) or during the course of the study, concurrent treatment with memantine; acetylcholinesterase inhibitors; antipsychotic agents (other than quetiapine) or mood stabilizers (e.g., valproate, lithium); or benzodiazepines (except as below).
• Low dose lorazepam (not more than 2 mg) may be used for sedation prior to MRI scans for those subjects requiring sedation. Neuropsychological testing may not be performed after lorazepam administration.
• Subjects who take short acting benzodiazepines (only temazepam or zolpidem are allowed) for sleep may continue to do so if they have been on a stable dose for 30 days prior to screening.
• Clonazepam may be used for treatment of dystonia or painful rigidity associated with PSP if the dose has been stable for 90 days prior to screening and is not expected to change during the course of the study.
• Treatment with lithium, methylene blue, tramiprosate, ketone bodies, latrepirdine, or any putative disease-modifying agent directed at tau within 90 days of screening (Visit 1).
• A history of alcohol or substance abuse within 1 year prior to screening (Visit 1) and deemed to be clinically significant by the site investigator.

Sponsors & Collaborators

• NeuroTau, Inc.: lead
• The Cleveland Clinic: collaborator

Study Sites (1)

Lou Ruvo Center for Brain Health - Cleveland Clinic Nevada

Las Vegas, Nevada, 89106, United States

Location

MeSH Terms

Conditions

Supranuclear Palsy, Progressive

Interventions

tolfenamic acid

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Ophthalmoplegia; Ocular Motility Disorders; Cranial Nerve Diseases; Tauopathies; Neurodegenerative Diseases; Paralysis; Neurologic Manifestations; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Nasser Zawia, PhD

  NeuroTau, Inc.

  STUDY DIRECTOR

• Marwan Sabbagh, MD

  NeuroTau, Inc.

  STUDY DIRECTOR

Central Study Contacts

Zoltan Mari, MD

CONTACT

702 483-6000; mariz@ccf.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This is a randomized, double-blind, placebo-controlled parallel group study.

Study Record Dates

• First Submitted: December 17, 2019
• First Posted: February 5, 2020
• Study Start: January 1, 2021
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: February 5, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)