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Safinamide for Levodopa-induced Dyskinesia (PD-LID)

Primary Purpose

Dyskinesia, Drug-Induced, Parkinson Disease

Status
Withdrawn
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Safinamide Methanesulfonate 150mg
Safinamide Methanesulfonate 100mg
Safinamide Methanesulfonate matching placebo
Sponsored by
Zambon SpA
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dyskinesia, Drug-Induced

Eligibility Criteria

30 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male and female participants aged 30 years and above at the time of signing the informed consent;
  2. 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);
  3. 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;
  4. A diagnosis of Parkinson's disease consistent with the UK PD Brain Bank Society and MDS Clinical Diagnostic Criteria;
  5. 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;
  6. 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;
  7. 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;
  8. 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
  9. 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.

Exclusion Criteria:

  1. Participants with secondary or atypical parkinsonian syndrome
  2. Participants with solely diphasic dyskinesia without peak dose dyskinesia
  3. History of neurosurgical procedure for Parkinson's disease, including stereotactic surgery and Deep Brain Stimulation (DBS).
  4. Treatment with monoamine oxidase inhibitors, amantadine pethidine, dextromethorphan, fluoxetine, fluvoxamine in the 8 weeks prior to the screening visit
  5. 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.
  6. 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
  7. History of major psychiatric disease eg bipolar disorder, severe depression, schizophrenia or other psychosis.
  8. Current history of Impulse Control Disorder
  9. History of drug and/or alcohol abuse within 12 months prior to screening (DSM-V criteria)
  10. History of dementia (DSM-V criteria) or cognitive impairment MMSE < 24 at screening
  11. 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.
  12. Moderate or severe hepatic impairment with transaminases >2 times upper limit of normal (ULN) or bilirubin 1.5 times ULN
  13. 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.
  14. Use of any investigational drug within 30 days prior to screening or 5 half-lives, whichever is the longest.
  15. Allergy/sensitivity or contraindications to the investigational medicinal product (IMP) or their excipients.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Placebo Comparator

    Arm Label

    Safinamide 100mg

    Safinamide 150mg

    Placebo

    Arm Description

    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

    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

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

    Outcomes

    Primary Outcome Measures

    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

    Secondary Outcome Measures

    Assess the effect of two doses of safinamide on ON time with No Dyskinesia
    Change from Baseline (Day 1 prior to start of study intervention) to Week 26 total daily ON time with No dyskinesia based on PD Home Diary. A PD home diary is used to score 5 different conditions : ASLEEP, OFF, ON (ie, had adequate control of PD symptoms) without dyskinesia, ON with non-troublesome dyskinesia, and ON with troublesome dyskinesia.
    Assess the effect of two doses of safinamide on ON time with non-troublesome dyskinesia
    Change from Baseline (48 hours prior to Day 1) to Week 26 based on PD Home Diary in total daily ON time with non-troublesome dyskinesia. A PD home diary is used to score 5 different conditions : ASLEEP, OFF, ON (ie, had adequate control of PD symptoms) without dyskinesia, ON with non-troublesome dyskinesia, and ON with troublesome dyskinesia.
    Assess the effect of two doses of safinamide on ON time with troublesome dyskinesia
    Change from Baseline (48 hours prior to Day 1) to Week 26 based on PD Home Diary in total daily ON time with troublesome dyskinesia. A PD home diary is used to score 5 different conditions : ASLEEP, OFF, ON (ie, had adequate control of PD symptoms) without dyskinesia, ON with non-troublesome dyskinesia, and ON with troublesome dyskinesia.
    To assess the effect of two doses of safinamide on ON time with any dyskinesia (troublesome or non-troublesome)
    Change from Baseline (48 hours prior to Day 1) to Week 26 based on PD Home Diary in total daily ON time with any dyskinesia (troublesome or non-troublesome). A PD home diary is used to score 5 different conditions : ASLEEP, OFF, ON (ie, had adequate control of PD symptoms) without dyskinesia, ON with non-troublesome dyskinesia, and ON with troublesome dyskinesia.
    To assess the effect of two doses of safinamide on sleep time
    Change from Baseline (48 hours prior to Day 1) to Week 26 based on PD Home Diary in total daily sleep time. A PD home diary is used to score 5 different conditions : ASLEEP, OFF, ON (ie, had adequate control of PD symptoms) without dyskinesia, ON with non-troublesome dyskinesia, and ON with troublesome dyskinesia.
    To assess the effect of two doses of safinamide on Movement Disorder Society-Sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score and sub-scores
    Change from Baseline (Day 1 prior to start of study intervention) to Week 26 in MDS-UPDRS total score and sub-scores. The MDS-UPDRS is divided into 4 parts. In each part, all items are rated on a scale from 0 (normal) to 4 (severe impairment); Part I assesses 15 items of non-motor aspects of experiences of daily living; Part II comprises 13 items evaluating the impact of PD on patients' activities of daily living (ADL) over the week prior to the visit such as speech, salivation, swallowing, eating, handwriting, dressing, turning in bed, walking; part III assesses the motor abilities in PD patients at the time of the visit; Part IV assesses motor complications of therapy, such as dyskinesias, motor fluctuations.
    To assess the effect of two doses of safinamide on Clinician Global Impression of Change (CGIc)
    Clinician Global Impression of Change (CGIc) at Week 26. CGI-C is a 7-point scale used by Investigator to rate patient's overall improvement using a range of responses from 1 (very much improved) through to 7 (very much worse).
    To assess the effect of two doses of safinamide on Patient Global Impression of Change (PGIc)
    Patient Global Impression of Change (CGIc) at Week 26. PGI-C is a 7-point scale depicting a patient's rating of overall improvement using a range of responses from 1 (very much improved) to 7 (very much worse).
    To assess the effect of two doses of safinamide on PDQ-39 summary index
    Change from Baseline (Day 1 prior to start of study intervention) to Week 26 in PDQ-39 summary index. The PDQ-39 is a specific tool to assess quality of life in PD. Comprises 39 items divided into eight dimensions: mobility, activities of daily living (ADLs), emotional well-being, stigma, social support, cognition, communication and physical discomfort, where scores range from 0-100, with the higher, the worse the perception of quality of life.

    Full Information

    First Posted
    June 12, 2019
    Last Updated
    June 15, 2020
    Sponsor
    Zambon SpA
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03987750
    Brief Title
    Safinamide for Levodopa-induced Dyskinesia (PD-LID)
    Official Title
    A Phase 3, Double-blind, Placebo-controlled, Parallel-group Study to Assess the Efficacy and Safety of 2 Doses of Safinamide Compared to Placebo in the Treatment of LID in PD Patients With Motor Fluctuations
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2019
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    drug development plan has been updated
    Study Start Date
    October 2019 (Anticipated)
    Primary Completion Date
    April 2021 (Anticipated)
    Study Completion Date
    May 2021 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Zambon SpA

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    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.
    Detailed Description
    Trial participation will be up to a maximum duration of 32 weeks and will comprise: Screening period (up to 4 weeks) for screening assessments; Two weeks titration period: participants randomized to the 100 mg study arm will receive 100 mg during Week 1 and throughout the rest of the study; participants randomized to the 150 mg study arm will receive 100 mg during Weeks 1 and 2 , and 150 mg from Week 3 and throughout the rest of the study; participants randomized to the placebo arm will receive identical placebo tablets. Twenty-four weeks maintenance period during which patients receive their randomized treatment as an adjunct to their standard anti-PD medications, which should remain unaltered. End of treatment evaluations will be performed at the end of Week 26 or at early discontinuation A telephone follow-up call will be performed 2 weeks after the end of treatment to assess adverse events and concomitant medications

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Dyskinesia, Drug-Induced, Parkinson Disease

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Safinamide 100mg
    Arm Type
    Experimental
    Arm Description
    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
    Arm Title
    Safinamide 150mg
    Arm Type
    Experimental
    Arm Description
    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
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Participants randomized to the placebo arm will receive Safinamide Methanesulfonate matching placebo film-coated tablets once daily (3 x placebo tablets)
    Intervention Type
    Drug
    Intervention Name(s)
    Safinamide Methanesulfonate 150mg
    Intervention Description
    150 mg (free base)
    Intervention Type
    Drug
    Intervention Name(s)
    Safinamide Methanesulfonate 100mg
    Intervention Description
    100 mg (free base)
    Intervention Type
    Drug
    Intervention Name(s)
    Safinamide Methanesulfonate matching placebo
    Intervention Description
    placebo
    Primary Outcome Measure Information:
    Title
    Assess the effect of two doses of safinamide on reducing levodopa-induced dyskinesia
    Description
    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
    Time Frame
    26 weeks
    Secondary Outcome Measure Information:
    Title
    Assess the effect of two doses of safinamide on ON time with No Dyskinesia
    Description
    Change from Baseline (Day 1 prior to start of study intervention) to Week 26 total daily ON time with No dyskinesia based on PD Home Diary. A PD home diary is used to score 5 different conditions : ASLEEP, OFF, ON (ie, had adequate control of PD symptoms) without dyskinesia, ON with non-troublesome dyskinesia, and ON with troublesome dyskinesia.
    Time Frame
    26 weeks
    Title
    Assess the effect of two doses of safinamide on ON time with non-troublesome dyskinesia
    Description
    Change from Baseline (48 hours prior to Day 1) to Week 26 based on PD Home Diary in total daily ON time with non-troublesome dyskinesia. A PD home diary is used to score 5 different conditions : ASLEEP, OFF, ON (ie, had adequate control of PD symptoms) without dyskinesia, ON with non-troublesome dyskinesia, and ON with troublesome dyskinesia.
    Time Frame
    26 weeks
    Title
    Assess the effect of two doses of safinamide on ON time with troublesome dyskinesia
    Description
    Change from Baseline (48 hours prior to Day 1) to Week 26 based on PD Home Diary in total daily ON time with troublesome dyskinesia. A PD home diary is used to score 5 different conditions : ASLEEP, OFF, ON (ie, had adequate control of PD symptoms) without dyskinesia, ON with non-troublesome dyskinesia, and ON with troublesome dyskinesia.
    Time Frame
    26 weeks
    Title
    To assess the effect of two doses of safinamide on ON time with any dyskinesia (troublesome or non-troublesome)
    Description
    Change from Baseline (48 hours prior to Day 1) to Week 26 based on PD Home Diary in total daily ON time with any dyskinesia (troublesome or non-troublesome). A PD home diary is used to score 5 different conditions : ASLEEP, OFF, ON (ie, had adequate control of PD symptoms) without dyskinesia, ON with non-troublesome dyskinesia, and ON with troublesome dyskinesia.
    Time Frame
    26 weeks
    Title
    To assess the effect of two doses of safinamide on sleep time
    Description
    Change from Baseline (48 hours prior to Day 1) to Week 26 based on PD Home Diary in total daily sleep time. A PD home diary is used to score 5 different conditions : ASLEEP, OFF, ON (ie, had adequate control of PD symptoms) without dyskinesia, ON with non-troublesome dyskinesia, and ON with troublesome dyskinesia.
    Time Frame
    26 weeks
    Title
    To assess the effect of two doses of safinamide on Movement Disorder Society-Sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score and sub-scores
    Description
    Change from Baseline (Day 1 prior to start of study intervention) to Week 26 in MDS-UPDRS total score and sub-scores. The MDS-UPDRS is divided into 4 parts. In each part, all items are rated on a scale from 0 (normal) to 4 (severe impairment); Part I assesses 15 items of non-motor aspects of experiences of daily living; Part II comprises 13 items evaluating the impact of PD on patients' activities of daily living (ADL) over the week prior to the visit such as speech, salivation, swallowing, eating, handwriting, dressing, turning in bed, walking; part III assesses the motor abilities in PD patients at the time of the visit; Part IV assesses motor complications of therapy, such as dyskinesias, motor fluctuations.
    Time Frame
    26 weeks
    Title
    To assess the effect of two doses of safinamide on Clinician Global Impression of Change (CGIc)
    Description
    Clinician Global Impression of Change (CGIc) at Week 26. CGI-C is a 7-point scale used by Investigator to rate patient's overall improvement using a range of responses from 1 (very much improved) through to 7 (very much worse).
    Time Frame
    26 weeks
    Title
    To assess the effect of two doses of safinamide on Patient Global Impression of Change (PGIc)
    Description
    Patient Global Impression of Change (CGIc) at Week 26. PGI-C is a 7-point scale depicting a patient's rating of overall improvement using a range of responses from 1 (very much improved) to 7 (very much worse).
    Time Frame
    26 weeks
    Title
    To assess the effect of two doses of safinamide on PDQ-39 summary index
    Description
    Change from Baseline (Day 1 prior to start of study intervention) to Week 26 in PDQ-39 summary index. The PDQ-39 is a specific tool to assess quality of life in PD. Comprises 39 items divided into eight dimensions: mobility, activities of daily living (ADLs), emotional well-being, stigma, social support, cognition, communication and physical discomfort, where scores range from 0-100, with the higher, the worse the perception of quality of life.
    Time Frame
    26 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    30 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: 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. Exclusion Criteria: 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.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Charlotte Keywood, MD
    Organizational Affiliation
    Zambon SpA
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Learn more about this trial

    Safinamide for Levodopa-induced Dyskinesia (PD-LID)

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