Effect of Safinamide on Parkinson's Disease Related Chronic Pain

NCT03841604 | Completed Phase 4 Results

• 2 other identifiers: Z7219M012017-002426-20
• Study Type: interventional
• Target: 94
• Locations: 5 countries
• Sites: 45

Brief Summary

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

Conditions

Idiopathic Parkinson Disease

Keywords

Parkinson disease; Safinamide

Outcome Measures

Primary Outcomes (2)

• Change From Baseline to Week 16 in Pain Severity (NRS-11 Scale) - Full Analysis Set

  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.

  Baseline and Week 16

• Change From Baseline to Week 16 in Pain Severity (NRS-11 Scale) - Per Protocol Set

  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.

  Baseline and Week 16

Secondary Outcomes (9)

• Number of Subjects With a Reduction of ≥2 Points in Pain Severity at Week 16, Compared to Baseline

  Week 16

• The Change From Baseline to Week 16 in the Clinical Global Impression of Change (CGI-C) Score for Pain

  Baseline and Week 16

• The Global Impression of Severity (CGI-S) Score for Pain at Week 16

  Baseline and Week 16

• The Change From Baseline to Week 16 in the Patient Global Impression of Change (PGI-C) Score for Pain

  Baseline and Week 16

• Number of Subjects With Concomitant Use of Pain Drugs at Different Timepoints

  Baseline, weeks 4, 8 and 16

Study Arms (2)

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.

Drug: Safinamide Methanesulfonate

Placebo

PLACEBO COMPARATOR

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.

Other: Safinamide methanesulfonate matching placebo

Interventions

Safinamide Methanesulfonate DRUG

50 mg, 100 mg

Also known as: Xadago

Experimental

Safinamide methanesulfonate matching placebo OTHER

50 mg, 100 mg

Also known as: Placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Zambon SpA: lead

Study Sites (45)

Medizinische Universitat Innsbruck

Innsbruck, 6020, Austria

Location

Institut für Neuroimmunologische und Neurodegenerative Erkrankungen

Vienna, 1220, Austria

Location

Hopital Gabriel Montpied

Clermont-Ferrand, 63000, France

Location

CHU de GRENOBLE

Grenoble, 38700, France

Location

Hopitaux de La Timone

Marseille, 13385, France

Location

Centre Hospitalier Universitaire de Nimes

Nîmes, 30900, France

Location

Hopital de Hautepierre

Strasbourg, 67200, France

Location

Hôpital Pierre-Paul Riquet

Toulouse, 31300, France

Location

St. Joseph Krankenhaus Berlin

Berlin, 13088, Germany

Location

Universitätsklinikum Carl Gustav Carus an der TU Dresden

Dresden, 01307, Germany

Location

Katholische Kliniken Ruhrhalbinsel GmbH

Essen, 45257, Germany

Location

Neurologische Praxis

Gera, 07551, Germany

Location

University Medicine Göttingen Germany

Göttingen, 37075, Germany

Location

Klinik Haag i. OB

Haag, 83527, Germany

Location

Universitätsklinikum Gießen und Marburg GmbH

Marburg, 35043, Germany

Location

Universitätsklinikum Münster

Münster, 48149, Germany

Location

NeuroPoint Akademie

Ulm, 89073, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Zambon Investigative Site

Chieti, 66013, Italy

Location

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Centro per la Malattia di Parkinson e i Disturbi del Movimento

Milan, 20126, Italy

Location

Ospedale San Raffaele S.r.l. - PPDS

Milan, 20133, Italy

Location

Azienda Ospedaliera Di Perugia

Perugia, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, 56124, Italy

Location

Istituto Neurologico Mediterraneo Neuromed

Pozzilli, 86077, Italy

Location

Fondazione PTV Policlinico Tor Vergata

Roma, 00133, Italy

Location

Ospedale San Giovanni Battista - ACISMOM

Roma, 00148, Italy

Location

IRCCS San Raffaele Pisana

Roma, 00163, Italy

Location

Azienda Ospedaliera Universitaria OO.RR. San Giovanni di Dio Ruggi d'Aragona

Salerno, 84084, Italy

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital de La Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Universitario Vall d'Hebrón - PPDS

Barcelona, 08035, Spain

Location

C.A.U de Burgos - Hospital Universitario de Burgos

Burgos, 09006, Spain

Location

Hospital Puerta del Mar

Cadiz, 11009, Spain

Location

Hospital Universitario de Donostia

Donostia / San Sebastian, 20014, Spain

Location

Hospital Universitario de La Princesa

Madrid, 28006, Spain

Location

Hospital Universitario La Paz - PPDS

Madrid, 28046, Spain

Location

Hospital Universitario Puerta de Hierro - Majadahonda

Madrid, 28222, Spain

Location

Hospital HM Puerta del Sur

Móstoles, 28938, Spain

Location

Clinica Universidad Navarra

Pamplona, 31008, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, 31008, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

safinamide

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Results Point of Contact

• Title: Elena Tiberio, BSc
• Organization: Zambon SpA

clinicaltrials@zambongroup.com

+39 02665241

Study Officials

• Charlotte Keywood, MD

  Zambon SpA

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2019
• First Posted: February 15, 2019
• Study Start: April 9, 2019
• Primary Completion: April 30, 2021
• Study Completion: May 3, 2021
• Last Updated: May 22, 2023
• Results First Posted: May 22, 2023

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (11); FR (6); AU (2); DE (10); ES (16)