Safinamide for Levodopa-induced Dyskinesia (PD-LID)

NCT03987750 | Withdrawn Phase 3 FDA Drug

• 1 other identifier: Z7219L04
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This will be a prospective, multi-center, randomized, double-blind, parallel group, placebo-controlled study, in participants with PD who are on a stable regimen of dopaminergic medication and have at least mild levodopa-induced dyskinesia. Eligible participants will be randomized to one of three treatment groups to receive adjunctive daily treatment with either safinamide 100 mg, safinamide 150 mg or placebo in a 1:1:1 ratio. Outcome will be assessed after 26 weeks of treatment.

Conditions

Dyskinesia, Drug-Induced; Parkinson Disease

Outcome Measures

Primary Outcomes (1)

• Assess the effect of two doses of safinamide on reducing levodopa-induced dyskinesia

  Change from Baseline to Week 26 in levodopa-induced dyskinesia based on UDysRS total score. The UDysRS is a dyskinesia rating scale from 0-104; it evaluates involuntary movements associated with PD. A higher score indicates more severe PD

  26 weeks

Secondary Outcomes (9)

• Assess the effect of two doses of safinamide on ON time with No Dyskinesia

  26 weeks

• Assess the effect of two doses of safinamide on ON time with non-troublesome dyskinesia

  26 weeks

• Assess the effect of two doses of safinamide on ON time with troublesome dyskinesia

  26 weeks

• To assess the effect of two doses of safinamide on ON time with any dyskinesia (troublesome or non-troublesome)

  26 weeks

• To assess the effect of two doses of safinamide on sleep time

  26 weeks

Study Arms (3)

Safinamide 100mg

EXPERIMENTAL

Participants randomized to the 100 mg study arm will receive 100 mg safinamide methanesulfonate film-coated tablets once daily during Week 1 (2 x 50 mg active tablets plus 1 placebo tablet) and throughout the rest of the study safinamide

Drug: Safinamide Methanesulfonate 100mg

Safinamide 150mg

EXPERIMENTAL

Participants randomized to the 150 mg study arm will receive 100 mg methanesulfonate film-coated tablets once daily during Weeks 1 and 2 (2 x 50 mg active tablets plus 1 placebo tablet), and 150 mg methanesulfonate film-coated tablets once daily(3 x 50 mg active tablets) from Week 3 and throughout the rest of the study

Drug: Safinamide Methanesulfonate 150mg

Placebo

PLACEBO COMPARATOR

Participants randomized to the placebo arm will receive Safinamide Methanesulfonate matching placebo film-coated tablets once daily (3 x placebo tablets)

Drug: Safinamide Methanesulfonate matching placebo

Interventions

Safinamide Methanesulfonate 150mg DRUG

150 mg (free base)

Safinamide 150mg

Safinamide Methanesulfonate 100mg DRUG

100 mg (free base)

Safinamide 100mg

Safinamide Methanesulfonate matching placebo DRUG

placebo

Placebo

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female participants aged 30 years and above at the time of signing the informed consent;
• Female participants may participate if they are not of child bearing potential (post-menopausal with no periods for at least one year, or surgically sterilized);
• Women of child bearing potential (WOCBP) may participate if they are not pregnant, not breastfeeding, and agree to follow the contraceptive guidance during the treatment period and for at least 30 days after the last dose of study intervention;
• A diagnosis of Parkinson's disease consistent with the UK PD Brain Bank Society and MDS Clinical Diagnostic Criteria;
• Levodopa immediate release and/or controlled release, given at least 3 times daily, on a stable regimen for at least 4 weeks prior to screening;
• Participants may also be taking benserazide, catcechol O methyl transferease (COMT) inhibitors and dopamine agonists, the dose of which must be stable for at least 4 weeks prior to screening;
• Predictable peak dose dyskinesia of at least mild severity and causing at least mild disability as defined as a score of ≥2 on the MDS UPDRS questions 4.1 and 4.2 at screening and at least two 30 minute periods of ON time with troublesome dyskinesia recorded in 24 hour PD home diaries performed in each of the two days prior to the randomization visit;
• Participants with motor fluctuations with at least three 30 minute periods in OFF (for a total of 1.5 hours per waking day) in each of the two consecutive 24 hour home diaries completed at the end of the screening period in the 48 hours prior to Day 1
• Provided written informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol, prior to the study screening procedures commencing.

You may not qualify if:

• Participants with secondary or atypical parkinsonian syndrome
• Participants with solely diphasic dyskinesia without peak dose dyskinesia
• History of neurosurgical procedure for Parkinson's disease, including stereotactic surgery and Deep Brain Stimulation (DBS).
• Treatment with monoamine oxidase inhibitors, amantadine pethidine, dextromethorphan, fluoxetine, fluvoxamine in the 8 weeks prior to the screening visit
• Concomitant use of selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic/tetracyclic antidepressants may be permitted but used at the lowest doses.
• Participants who are unable to complete the home diary and have 2 consecutive 24-hour periods with more than 4 missing periods per 24 hours in the diary, completed at the end of the screening period, in the 48 hours prior to Day 1
• History of major psychiatric disease eg bipolar disorder, severe depression, schizophrenia or other psychosis.
• Current history of Impulse Control Disorder
• History of drug and/or alcohol abuse within 12 months prior to screening (DSM-V criteria)
• History of dementia (DSM-V criteria) or cognitive impairment MMSE \< 24 at screening
• Ophthalmologic history of the following conditions: albinism, uveitis, retinitis pigmentosa, retinal degeneration, active retinopathy, severe progressive diabetic retinopathy, inherited retinopathy or family history of hereditary retinal disease.
• Moderate or severe hepatic impairment with transaminases \>2 times upper limit of normal (ULN) or bilirubin 1.5 times ULN
• Any clinically significant or unstable medical or surgical condition that, in the opinion of the investigator, might preclude safe completion of the study or might affect the results of the study.
• Use of any investigational drug within 30 days prior to screening or 5 half-lives, whichever is the longest.
• Allergy/sensitivity or contraindications to the investigational medicinal product (IMP) or their excipients.

Sponsors & Collaborators

• Zambon SpA: lead

MeSH Terms

Conditions

Dyskinesia, Drug-Induced; Parkinson Disease

Interventions

safinamide

Condition Hierarchy (Ancestors)

Dyskinesias; Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurotoxicity Syndromes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Poisoning; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Charlotte Keywood, MD

  Zambon SpA

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2019
• First Posted: June 17, 2019
• Study Start: October 1, 2019
• Primary Completion: April 1, 2021
• Study Completion: May 1, 2021
• Last Updated: June 17, 2020

Record last verified: 2019-06