- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03841604
Effect of Safinamide on Parkinson's Disease Related Chronic Pain
A Randomised, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Safinamide 100mg Once Daily, as add-on Therapy, in Idiopathic Parkinson's Disease (PD) Patients With Motor Fluctuations and PD Related Chronic Pain
Primary objective:
• To evaluate the potential efficacy of safinamide 100 mg once daily (OD), compared with placebo, as add-on therapy for PD-related chronic pain
Secondary objectives:
- Percentage of pain responders
- Clinical Global Impression for pain
- Patient Global Impression for pain
- Reduction in use of pain drugs
- Mood
- Motor and non-motor symptoms
Safety Objectives:
• Safety and tolerability
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a Phase IV, international, multicentre, randomised, double-blind, placebo controlled study in idiopathic Parkinson's disease (IPD) patients, experiencing motor fluctuations and PD-related chronic pain while on stable doses of levodopa (L-Dopa), to Evaluate the Efficacy and Safety of Safinamide 100 mg Once Daily, as Add-On Therapy.
The study consisted of:
- A screening period of up to 1 to 2 weeks.
- A treatment period of 16 weeks.
- A telephone follow-up call at 1 week after the end of treatment. Eligible subjects were randomly assigned in a ratio of 2:1 to receive either safinamide (50 mg or 100 mg) or matching placebo. At Day 1, eligible subjects entered the treatment period to receive safinamide 50 mg (from Day 1 to Day 7) and then 100 mg (from Day 8 onwards) orally OD. After completion of all baseline assessments, subjects received the first dose of study drug at the study center and, thereafter, study drug was to be taken at home each morning along with their first morning dose of L-DOPA and other (if any) PD medications. On Day 8, the dose of study drug was increased, at home, to 100 mg OD. Each subject received treatment for 16 weeks, with visits at Week 0/Day 1 (baseline) and at Weeks 4, 8, and 16 (or early termination). From Day 1 onwards, subjects recorded the use of as-needed (PRN) medications along with indicating the worst pain they experienced on a daily basis.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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Innsbruck, Austria, 6020
- Medizinische Universität Innsbruck
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Wien, Austria, 1220
- Institut für Neuroimmunologische und Neurodegenerative Erkrankungen
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Clermont-Ferrand, France, 63000
- Hopital Gabriel Montpied
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Grenoble, France, 38700
- CHU de Grenoble
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Marseille, France, 13385
- Hopitaux de La Timone
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Nîmes, France, 30900
- Centre Hospitalier Universitaire de Nīmes
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Strasbourg, France, 67200
- Hopital de Hautepierre
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Toulouse, France, 31300
- Hôpital Pierre-Paul Riquet
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Berlin, Germany, 13088
- St. Joseph Krankenhaus Berlin
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Dresde, Germany, 01307
- Universitätsklinikum Carl Gustav Carus an der TU Dresden
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Essen, Germany, 45257
- Katholische Kliniken Ruhrhalbinsel GmbH
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Gera, Germany, 07551
- Neurologische Praxis
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Göttingen, Germany, 37075
- University Medicine Göttingen Germany
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Haag, Germany, 83527
- Klinik Haag i. OB
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Marburg, Germany, 35043
- Universitätsklinikum Gießen und Marburg GmbH
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Münster, Germany, 48149
- Universitätsklinikum Münster
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Ulm, Germany, 89081
- Universitätsklinikum Ulm
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Ulm, Germany, 89073
- NeuroPoint Akademie
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Chieti, Italy, 66013
- Zambon Investigative Site
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Milano, Italy, 20122
- Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
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Milano, Italy, 20126
- Centro per la Malattia di Parkinson e i Disturbi del Movimento
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Milano, Italy, 20133
- Ospedale San Raffaele S.r.l. - PPDS
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Perugia, Italy
- Azienda Ospedaliera di Perugia
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Pisa, Italy, 56124
- Azienda Ospedaliero Universitaria Pisana
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Pozzilli, Italy, 86077
- Istituto Neurologico Mediterraneo Neuromed
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Roma, Italy, 00163
- IRCCS San Raffaele Pisana
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Roma, Italy, 00133
- Fondazione PTV Policlinico Tor Vergata
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Roma, Italy, 00148
- Ospedale San Giovanni Battista - ACISMOM
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Salerno, Italy, 84084
- Azienda Ospedaliera Universitaria OO.RR. San Giovanni di Dio Ruggi d'Aragona
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Barcelona, Spain, 08003
- Hospital del Mar
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Barcelona, Spain, 08025
- Hospital de la Santa Creu I Sant Pau
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Barcelona, Spain, 08035
- Hospital Universitario Vall d'Hebron - PPDS
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Burgos, Spain, 09006
- C.A.U de Burgos - Hospital Universitario de Burgos
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Cadiz, Spain, 11009
- Hospital Puerta del Mar
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Donostia, Spain, 20014
- Hospital Universitario de Donostia
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Madrid, Spain, 28006
- Hospital Universitario de La Princesa
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Madrid, Spain, 28222
- Hospital Universitario Puerta de Hierro - Majadahonda
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Madrid, Spain, 28046
- Hospital Universitario La Paz - PPDS
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Móstoles, Spain, 28938
- Hospital HM Puerta del Sur
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Pamplona, Spain, 31008
- Complejo Hospitalario de Navarra
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Pamplona, Spain, 31008
- Clinica Universidad Navarra
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Sevilla, Spain, 41009
- Hospital Universitario Virgen Macarena
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Sevilla, Spain, 41013
- Hospital Universitario Virgen del Rocio
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Valencia, Spain, 46026
- Hospital Universitari i Politecnic La Fe de Valencia
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Zaragoza, Spain, 50009
- Hospital Universitario Miguel Servet
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Participant must be 30 years of age or older, at the time of signing the informed consent.
- Diagnosed with IPD by using the United Kingdom Parkinson's Disease Society Brain Bank criteria for more than 5 years duration.
- Receiving treatment with a stable dose of oral L-Dopa (including controlled release [CR], immediate release [IR] or a combination of CR/IR), with and without benserazide/carbidopa, with or without addition of a catechol O-methyltransferase (COMT) inhibitor and may be receiving concomitant treatment with stable doses of a dopamine agonist, an anticholinergic and/or amantadine for at least 4 weeks prior to the randomisation (baseline visit).
- Hoehn and Yahr stage between 2-3 (inclusive) during the "ON" phase at the screening visit.
- Experiencing motor fluctuations following optimum titration of treatment medications and within the 4 weeks immediately prior to randomisation.
- Experiencing chronic pain (i.e. ongoing for ≥3 months prior to screening visit); the Investigator must consider chronic pain directly related to PD and not explained by any other health problem (e.g. peripheral neuropathy, organ disease or arthritis pain) OR consider the intensity of chronic pain specifically aggravated by PD.
- If taking regular analgesics, the treatment regimen should be stable in the 4 weeks prior to the randomisation visit.
- Able to maintain an accurate and complete electronic diary with the help of a caregiver.
Male or female
•A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: i.Not a woman of childbearing potential (WOCBP) OR ii.A WOCBP who agrees to follow the contraceptive guidance
- Capable of giving signed informed consent
Exclusion Criteria:
- Any form of Parkinsonism other than IPD.
- Diagnosis of chronic migraine (>15 days per month) or cancer pain.
- History of bipolar disorder, depression, schizophrenia or other psychotic disorder requiring treatment with neuroleptics.
- History of dementia or cognitive dysfunction.
- Severe, peak dose or biphasic dyskinesia.
- Unpredictable or widely swinging fluctuations.
- Ophthalmologic history including any 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 liver failure using the Child-Pugh classification score.
- History of drug and/or alcohol abuse within 12 months prior to screening as defined by the current edition of the Diagnostic and Statistical Manual of Mental Disorders.
- Allergy/sensitivity, intolerance or contraindications to Safinamide.
- Treatment with monoamine oxidase inhibitors (MAOIs), levodopa infusion, pethidine, fluoxetine, fluvoxamine less than 4 weeks prior to the randomisation visit
- Use of any investigational drug or device within 30 days prior to screening or 5 half-lives, whichever is the longest
- Previous treatment with Safinamide in the 9 months before the screening visit
- Mini-Mental State Exam (MMSE) total score <24 at screening.
- NRS score ≤ 4 points at randomization visit.
- Any clinically significant condition which, in the opinion of the Investigator, would not be compatible with study participation or represent a risk for participants while in the study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Experimental
Safinamide methanesulfonate film coated tablets once daily, 50 mg and 100 mg. Safinamide methanesulfonate 50 mg and 100 mg tablets was administered orally, OD, with or without food, at breakfast time when the subject was taking their morning dose of L-DOPA. Subjects received study drug 50 mg (from Day 1 to Day 7) and then 100 mg (from Day 8 onwards). The dose of 100 mg/day (titrated from 50 mg/day after 1 week) was selected based on the results of previous studies in patients with PD and from the results of a post hoc analysis that investigated the effects of safinamide on pain. |
50 mg, 100 mg
Other Names:
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Placebo Comparator: Placebo
Safinamide methanesulfonate matching placebo film coated tablets once daily.
The matching placebo was administered orally, OD, in tablets, with or without food, at breakfast time when the subject was taking their morning dose of L-DOPA.
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50 mg, 100 mg
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change From Baseline to Week 16 in Pain Severity (NRS-11 Scale) - Full Analysis Set
Time Frame: Baseline and Week 16
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To evaluate the potential efficacy of safinamide 100 (mg od), compared to placebo, as add-on therapy, for change pain severity ("average worst pain experienced in the last 7 days"), as assessed by an 11-point Numerical Rating Scale (NRS).
Based on this scale, 0 point is the minimum and 10 point is the maximum.
The higher the score, the more severe the pain.
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Baseline and Week 16
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Change From Baseline to Week 16 in Pain Severity (NRS-11 Scale) - Per Protocol Set
Time Frame: Baseline and Week 16
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To evaluate the potential efficacy of safinamide 100 (mg od), compared to placebo, as add-on therapy, for change pain severity ("average worst pain experienced in the last 7 days"), as assessed by an 11-point Numerical Rating Scale (NRS).
Based on this scale, 0 point is the minimum and 10 point is the maximum.
The higher the score, the more severe the pain.
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Baseline and Week 16
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Subjects With a Reduction of ≥2 Points in Pain Severity at Week 16, Compared to Baseline
Time Frame: Week 16
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Reduction in pain severity (based on the "average worst pain experienced in the last 7 days") of ≥ 2 points was assessed by an 11-point NRS (numerical rating scale), compared to baseline.
Based on this scale, 0 point is the minimum and 10 point is the maximum.
The higher the score, the more severe the pain.
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Week 16
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The Change From Baseline to Week 16 in the Clinical Global Impression of Change (CGI-C) Score for Pain
Time Frame: Baseline and Week 16
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CGI-C (Clinical Global Impression - Change) score for pain is a seven-point scale that indicates the patient's impression of change for relevant symptoms. It ranges from "substantial improvement" to "substantial worsening":
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Baseline and Week 16
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The Global Impression of Severity (CGI-S) Score for Pain at Week 16
Time Frame: Baseline and Week 16
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The CGI-S (Clinical Global Impression - Severity) score is a seven-point scale which asks the clinician one question: "considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" which is rated as follow:
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Baseline and Week 16
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The Change From Baseline to Week 16 in the Patient Global Impression of Change (PGI-C) Score for Pain
Time Frame: Baseline and Week 16
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The Patients' Global Impression of Change (PGI-C) scale is designed to capture the subject's perception of change in activity limitations, symptoms, emotions, an overall quality of life. These areas are captured using a 7- point scale, indicating:
Of course, the higher the score, the better the outcome. |
Baseline and Week 16
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Number of Subjects With Concomitant Use of Pain Drugs at Different Timepoints
Time Frame: Baseline, weeks 4, 8 and 16
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This outcome describes the number of subjects which had concomitant assumption of pain drugs at different timepoints.
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Baseline, weeks 4, 8 and 16
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Amount of PRN PD Pain Medication: Count of Subjects Who Used PRN PD Pain Medication in the 7 Days Preceding Visits
Time Frame: at Baseline and weeks 4, 8 and 16
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Total count of patients who used PRN (meaning "when necessary") Parkinson's Disease Pain Medications was expressed both in number and in percentage. The analysis of amount of concomitant PRN PD pain medications as reported in the subject diary was summarized:
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at Baseline and weeks 4, 8 and 16
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Amount of PRN PD Pain Medication: Number of Days on Which PRN PD Pain Medication Was Taken at Different Timepoints
Time Frame: At Baseline and weeks 4, 8 and 16
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The analysis of amount of concomitant PRN PD pain medications as reported in the subject diary was summarized:
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At Baseline and weeks 4, 8 and 16
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Change From Baseline to Week 16 in the Hospital Anxiety and Depression Scale (HADS) Score
Time Frame: Baseline and Week 16
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The Hospital Anxiety and Depression Scale (HADS) was devised to measure anxiety and depression in a general medical population of patients through a unique questionnaire which takes 2-5 min to be completed. The questionnaire consists of a total of 14 items: seven items for the anxiety subscale (HADS Anxiety) and seven items for the depression subscale (HADS Depression). HADS Anxiety focus mainly on symptoms of generalized anxiety disorder and HADS Depression is focused on anhedonia, the main symptom of depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for anxiety subscale and the same for depression subscale, where: 0-7 = Normal 8-10 = Borderline abnormal (borderline case). 11-21 = Abnormal (case) The two subscores are then summed up to obtain a total Hospital Anxiety and Depression Scale (HADS). The total scale range is 0-42. The higher the score, the worse the anxiety/depression status. |
Baseline and Week 16
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The Change From Baseline to Week 16 in MDS-UPDRS
Time Frame: Baseline and Week 16
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Change in the MDS-UPDRS = Movement Disorder Society-Unified Parkinson's Disease Rating Scale The MDS-UPDRS is defined by 4 Parts, each composed by a different number of items.
Each item is rated on a 5-point Likert-type scale (ranging from 0 to 4); Part I (non-motor experiences of daily living; 13 items) Part II (motor experiences of daily living;13 items) Part III (motor examination; 33 items) Part IV (motor complications; 6 items) The MDS-UPDRS has a minimum score of 0 and a maximum score of 260.
The higher the score, the more severe the impairment.
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Baseline and Week 16
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Charlotte Keywood, MD, Zambon SpA
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- Z7219M01
- 2017-002426-20 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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