Dyskinesia, Drug-InducedPhase 3NCT03987750
Safinamide for Levodopa-induced Dyskinesia (PD-LID)
A Phase 3 study testing Safinamide Methanesulfonate 150mg and Safinamide Methanesulfonate 100mg in people with Dyskinesia, Drug-Induced and Parkinson Disease, run by Zambon SpA.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 years and older
- Conditions the study is for
- Dyskinesia, Drug-Induced, Parkinson Disease
- What is being tested?
- Safinamide Methanesulfonate 150mg and Safinamide Methanesulfonate 100mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Oct 2019to May 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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
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- 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.
About this study
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
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.
Read the 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
- Conditions
- Dyskinesia, Drug-Induced, Parkinson Disease
- Being tested
- Safinamide Methanesulfonate 150mg, Safinamide Methanesulfonate 100mg, Safinamide Methanesulfonate matching placebo
- Medical subject headings
- Dyskinesia, Drug-Induced, Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Safinamide Methanesulfonate 150mgDrug
150 mg (free base)
Safinamide Methanesulfonate 100mgDrug
100 mg (free base)
Safinamide Methanesulfonate matching placeboDrug
placebo
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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) Receives: Drug: Safinamide Methanesulfonate matching placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 26 weeks
Secondary outcomes (9)
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.
Measured: 26 weeks
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.
Measured: 26 weeks
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.
Measured: 26 weeks
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.
Measured: 26 weeks
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.
Measured: 26 weeks
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.
Measured: 26 weeks
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).
Measured: 26 weeks
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).
Measured: 26 weeks
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.
Measured: 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2019
- Study startOct 2019 (estimated)
- Primary completionApr 2021 (estimated)
- Study completionMay 2021 (estimated)
Why it stopped: drug development plan has been updated
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Dyskinesia, Drug-InducedStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zambon SpA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Charlotte Keywood, MD, Study director, Zambon SpA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03987750
- Sponsor's protocol ID
- Z7219L04
- Status last verified
- Jun 2019
- First submitted
- 12 Jun 2019
- Last updated
- 17 Jun 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03987750
- Acronym / sponsor ID
- Z7219L04
- Conditions
- Dyskinesia, Drug-Induced, Parkinson Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: drug development plan has been updated
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Zambon SpAIndustry (pharma, biotech, devices)
- Study start
- Oct 2019 (estimated)
- Primary completion
- Apr 2021 (estimated)
- Study completion
- May 2021 (estimated)
- First posted
- 17 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Safinamide 100mg | Experimental | Drug: Safinamide Methanesulfonate 100mgParticipants 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 |
| Safinamide 150mg | Experimental | Drug: Safinamide Methanesulfonate 150mgParticipants 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 |
| Placebo | Placebo comparator | Drug: Safinamide Methanesulfonate matching placeboParticipants randomized to the placebo arm will receive Safinamide Methanesulfonate matching placebo film-coated tablets once daily (3 x placebo tablets) |
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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;
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Safinamide Methanesulfonate 150mg150 mg (free base) | Drug | Safinamide 150mg |
| Safinamide Methanesulfonate 100mg100 mg (free base) | Drug | Safinamide 100mg |
| Safinamide Methanesulfonate matching placeboplacebo | Drug | Placebo |
Primary outcome
Assess the effect of two doses of safinamide on reducing levodopa-induced dyskinesia
Time frame: 26 weeks
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
9 secondary outcomes
Assess the effect of two doses of safinamide on ON time with No Dyskinesia
Time frame: 26 weeks
Assess the effect of two doses of safinamide on ON time with non-troublesome dyskinesia
Time frame: 26 weeks
Assess the effect of two doses of safinamide on ON time with troublesome dyskinesia
Time frame: 26 weeks
To assess the effect of two doses of safinamide on ON time with any dyskinesia (troublesome or non-troublesome)
Time frame: 26 weeks
To assess the effect of two doses of safinamide on sleep time
Time frame: 26 weeks
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
Time frame: 26 weeks
To assess the effect of two doses of safinamide on Clinician Global Impression of Change (CGIc)
Time frame: 26 weeks
To assess the effect of two doses of safinamide on Patient Global Impression of Change (PGIc)
Time frame: 26 weeks
To assess the effect of two doses of safinamide on PDQ-39 summary index
Time frame: 26 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charlotte Keywood, MD study director
Zambon SpA
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Safinamide Methanesulfonate 150mg and Safinamide Methanesulfonate 100mg in people with Dyskinesia, Drug-Induced and Parkinson Disease, run by Zambon SpA.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 17 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assess the effect of two doses of safinamide on reducing levodopa-induced dyskinesia (time frame: 26 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2020.