Safety and Tolerability of Perampanel in Cervical Dystonia

NCT02131467 | Completed Phase 1 FDA Drug

• 1 other identifier: 17-5864.4
• Study Type: interventional
• Target: 25
• Locations: 2 countries
• Sites: 5

Brief Summary

Cervical dystonia (CD) is the most common focal dystonia. Currently there are no effective oral medications for the treatment of CD. While botulinum toxin injections improve symptoms, they require repeated injections by a trained physician and some patients stop responding to injections or never respond at all. Therefore, alternative treatment options for CD are needed. One new agent is a drug that targets glutamate receptors that are thought to be involved dystonia. This drug, perampanel, was originally developed for epilepsy and is licensed for use in the USA and Canada for treating epilepsy. The purpose of this study is to test the effectiveness of perampanel in treating the symptoms of CD.

Conditions

Cervical Dystonia

Outcome Measures

Primary Outcomes (1)

• Number of subjects able to remain on study drug for minimum of 4 weeks.

  Tolerability will be assessed by counting number of subjects able to remain on drug

  Measured at week 12.

Secondary Outcomes (1)

• Safety will be evaluated as the cumulative number of new adverse events collected at each visit from Baseline to visit 4

  Adverse events at study visits weeks 0, 2, 6, 8, 9, 10 and 12

Other Outcomes (3)

• Change from baseline to end of maintenance in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)

  week 12

• CDIP58

  week 12

• CGI

  week 12

Study Arms (1)

Perampanel

EXPERIMENTAL

Perampanel 2 mg tablets will be initiated once daily at bedtime. The dose will be titrated over 6 weeks starting at 2 mg OD at baseline visit for 1 week, followed by 2mg increases every 1 week to a maximum of 12 mg/day. If side effects occur then patients will be decreased to previous dose level. If unable to tolerate increases, patients will enter the maintenance phase at previously tolerated dose, for minimum 4 weeks. Patients reaching 12 mg (maximal dose) will be maintained at that dose for 4 weeks. Taper will be over 2 weeks 1 tablet every 2 days from a maximum of 6 tablets per day to stop.

Drug: Perampanel

Interventions

Perampanel DRUG

oral drug

Perampanel

Eligibility Criteria

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

You may qualify if:

• 18-65 year old male and female patients with primary cervical dystonia.
• Subject may be untreated with botulinum toxin; treated with botulinum toxin but who are at least 8 weeks (+ 1 week) from a previous injection; or who have experienced an insufficient response to botulinum toxin in the opinion of the enrolling investigator. Note: We will aim to include subjects who have a stable response that lasts 12 weeks or longer.
• Subjects may be on stable anti-dystonia treatment (for at least one month) including anticholinergics, baclofen, and anxiolytics including benzodiazepines.

You may not qualify if:

• Secondary cervical dystonia,
• Significant dystonia in body areas other than cervical region,
• Cognitive impairment (e.g., Montreal Cognitive assessment (MOCA) \< 26);
• Active psychosis;
• History of aggression;
• Active depression (Hamilton Depression Rating Scale (HDRS) score ≥ 12).
• Current abuse of alcohol or subjects who do not agree to avoid alcohol during treatment,
• Substance abuse (current or prior);
• Active infection,
• Hypersensitivity to perampanel,
• Significant renal dysfunction (Creatinine clearance \< 50ml/min),
• Significant laboratory abnormalities (ALT or AST greater than twice normal value; elevated bilirubin, active liver disease: hepatitis, cholestasis, cirrhosis, etc.),
• Significant medical illness,
• Women who are pregnant or plan to become pregnant, women who are breastfeeding,
• Subjects who do not agree to avoid consumption of grapefruit or grapefruit-containing products throughout the study,

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Dystonia Study Group: collaborator

Study Sites (5)

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Beth Israel Medical Center

New York, New York, 10003, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Toronto Western Hospital

Toronto, Ontario, M5T 2S8, Canada

Location

MeSH Terms

Conditions

Torticollis

Interventions

perampanel

Condition Hierarchy (Ancestors)

Dystonia; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Susan H Fox, MRCP(UK), PhD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2014
• First Posted: May 6, 2014
• Study Start: September 1, 2017
• Primary Completion: February 28, 2020
• Study Completion: February 28, 2020
• Last Updated: April 7, 2020

Record last verified: 2020-04

Locations

US (4); CA (1)