Effect of Safinamide on Parkinson's Disease Related Chronic Pain

NCT ID: NCT03841604

Last Updated: 2023-05-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-09
• Study Completion Date: 2021-05-03

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

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.

Conditions

Idiopathic Parkinson Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Safinamide Methanesulfonate

Intervention Type: DRUG

50 mg, 100 mg

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.

Group Type: PLACEBO_COMPARATOR

Safinamide methanesulfonate matching placebo

Intervention Type: OTHER

50 mg, 100 mg

Interventions

Safinamide Methanesulfonate

50 mg, 100 mg

Intervention Type: DRUG

Safinamide methanesulfonate matching placebo

50 mg, 100 mg

Intervention Type: OTHER

Other Intervention Names

Xadago; Placebo

Eligibility Criteria

Inclusion Criteria

1. Participant must be 30 years of age or older, at the time of signing the informed consent.

2. Diagnosed with IPD by using the United Kingdom Parkinson's Disease Society Brain Bank criteria for more than 5 years duration.

3. 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).

4. Hoehn and Yahr stage between 2-3 (inclusive) during the "ON" phase at the screening visit.

5. Experiencing motor fluctuations following optimum titration of treatment medications and within the 4 weeks immediately prior to randomisation.

6. 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.

7. If taking regular analgesics, the treatment regimen should be stable in the 4 weeks prior to the randomisation visit.

8. Able to maintain an accurate and complete electronic diary with the help of a caregiver.

9. 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

10. Capable of giving signed informed consent

Exclusion Criteria

1. Any form of Parkinsonism other than IPD.

2. Diagnosis of chronic migraine (>15 days per month) or cancer pain.

3. History of bipolar disorder, depression, schizophrenia or other psychotic disorder requiring treatment with neuroleptics.

4. History of dementia or cognitive dysfunction.

5. Severe, peak dose or biphasic dyskinesia.

6. Unpredictable or widely swinging fluctuations.

7. 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.

8. Moderate or severe liver failure using the Child-Pugh classification score.

9. 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.

10. Allergy/sensitivity, intolerance or contraindications to Safinamide.

11. Treatment with monoamine oxidase inhibitors (MAOIs), levodopa infusion, pethidine, fluoxetine, fluvoxamine less than 4 weeks prior to the randomisation visit

12. Use of any investigational drug or device within 30 days prior to screening or 5 half-lives, whichever is the longest

13. Previous treatment with Safinamide in the 9 months before the screening visit

14. Mini-Mental State Exam (MMSE) total score <24 at screening.

15. NRS score ≤ 4 points at randomization visit.

16. 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

• Minimum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zambon SpA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Charlotte Keywood, MD

Role: STUDY_DIRECTOR

Zambon SpA

Locations

Medizinische Universitat Innsbruck

Innsbruck, , Austria

Institut für Neuroimmunologische und Neurodegenerative Erkrankungen

Vienna, , Austria

Hopital Gabriel Montpied

Clermont-Ferrand, , France

CHU de GRENOBLE

Grenoble, , France

Hopitaux de La Timone

Marseille, , France

Centre Hospitalier Universitaire de Nimes

Nîmes, , France

Hopital de Hautepierre

Strasbourg, , France

Hôpital Pierre-Paul Riquet

Toulouse, , France

St. Joseph Krankenhaus Berlin

Berlin, , Germany

Universitätsklinikum Carl Gustav Carus an der TU Dresden

Dresden, , Germany

Katholische Kliniken Ruhrhalbinsel GmbH

Essen, , Germany

Neurologische Praxis

Gera, , Germany

University Medicine Göttingen Germany

Göttingen, , Germany

Klinik Haag i. OB

Haag, , Germany

Universitätsklinikum Gießen und Marburg GmbH

Marburg, , Germany

Universitätsklinikum Münster

Münster, , Germany

NeuroPoint Akademie

Ulm, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

Zambon Investigative Site

Chieti, , Italy

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, , Italy

Centro per la Malattia di Parkinson e i Disturbi del Movimento

Milan, , Italy

Ospedale San Raffaele S.r.l. - PPDS

Milan, , Italy

Azienda Ospedaliera Di Perugia

Perugia, , Italy

Azienda Ospedaliero Universitaria Pisana

Pisa, , Italy

Istituto Neurologico Mediterraneo Neuromed

Pozzilli, , Italy

Fondazione PTV Policlinico Tor Vergata

Roma, , Italy

Ospedale San Giovanni Battista - ACISMOM

Roma, , Italy

IRCCS San Raffaele Pisana

Roma, , Italy

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

Salerno, , Italy

Hospital del Mar

Barcelona, , Spain

Hospital de La Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Universitario Vall d'Hebrón - PPDS

Barcelona, , Spain

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

Burgos, , Spain

Hospital Puerta del Mar

Cadiz, , Spain

Hospital Universitario de Donostia

Donostia / San Sebastian, , Spain

Hospital Universitario de La Princesa

Madrid, , Spain

Hospital Universitario La Paz - PPDS

Madrid, , Spain

Hospital Universitario Puerta de Hierro - Majadahonda

Madrid, , Spain

Hospital HM Puerta del Sur

Móstoles, , Spain

Clinica Universidad Navarra

Pamplona, , Spain

Complejo Hospitalario de Navarra

Pamplona, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, , Spain

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Countries

Austria; France; Germany; Italy; Spain

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-002426-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Z7219M01

Identifier Type: -

Identifier Source: org_study_id