Clinical trial NCT03841604: Effect of Safinamide on Parkinson's Disease Related Chronic Pain
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Idiopathic Parkinson Disease
Keywords: Parkinson disease
Safinamide
Lead sponsor: Zambon SpA
Sponsor class: INDUSTRY
First posted: 2019-02-15
Enrollment: 94
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change From Baseline to Week 16 in Pain Severity (NRS-11 Scale) - Full Analysis Set
timeFrame: Baseline and Week 16
measure: Change From Baseline to Week 16 in Pain Severity (NRS-11 Scale) - Per Protocol Set
timeFrame: Baseline and Week 16
Secondary outcomes:
measure: Number of Subjects With a Reduction of ≥2 Points in Pain Severity at Week 16, Compared to Baseline
timeFrame: Week 16
measure: The Change From Baseline to Week 16 in the Clinical Global Impression of Change (CGI-C) Score for Pain
timeFrame: Baseline and Week 16
measure: The Global Impression of Severity (CGI-S) Score for Pain at Week 16
timeFrame: Baseline and Week 16
measure: The Change From Baseline to Week 16 in the Patient Global Impression of Change (PGI-C) Score for Pain
timeFrame: Baseline and Week 16
measure: Number of Subjects With Concomitant Use of Pain Drugs at Different Timepoints
timeFrame: Baseline, weeks 4, 8 and 16
measure: Amount of PRN PD Pain Medication: Count of Subjects Who Used PRN PD Pain Medication in the 7 Days Preceding Visits
timeFrame: at Baseline and weeks 4, 8 and 16
measure: Amount of PRN PD Pain Medication: Number of Days on Which PRN PD Pain Medication Was Taken at Different Timepoints
timeFrame: At Baseline and weeks 4, 8 and 16
measure: Change From Baseline to Week 16 in the Hospital Anxiety and Depression Scale (HADS) Score
timeFrame: Baseline and Week 16
measure: The Change From Baseline to Week 16 in MDS-UPDRS
timeFrame: Baseline and Week 16
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medizinische Universitat Innsbruck
city: Wien
country: Austria
facility: Institut für Neuroimmunologische und Neurodegenerative Erkrankungen
city: Clermont-Ferrand
country: France
facility: Hopital Gabriel Montpied
city: Grenoble
country: France
facility: CHU de GRENOBLE
city: Marseille
country: France
facility: Hopitaux de La Timone
city: Nîmes
country: France
facility: Centre Hospitalier Universitaire de Nimes
city: Strasbourg
country: France
facility: Hopital de Hautepierre
city: Toulouse
country: France
facility: Hôpital Pierre-Paul Riquet
city: Berlin
country: Germany
facility: St. Joseph Krankenhaus Berlin
city: Dresde
country: Germany
facility: Universitätsklinikum Carl Gustav Carus an der TU Dresden
city: Essen
country: Germany
facility: Katholische Kliniken Ruhrhalbinsel GmbH
city: Gera
country: Germany
facility: Neurologische Praxis
city: Göttingen
country: Germany
facility: University Medicine Göttingen Germany
city: Haag
country: Germany
facility: Klinik Haag i. OB
city: Marburg
country: Germany
facility: Universitätsklinikum Gießen und Marburg GmbH
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Ulm
country: Germany
facility: NeuroPoint Akademie
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Chieti
country: Italy
facility: Zambon Investigative Site
city: Milano
country: Italy
facility: Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
city: Milano
country: Italy
facility: Centro per la Malattia di Parkinson e i Disturbi del Movimento
city: Milano
country: Italy
facility: Ospedale San Raffaele S.r.l. - PPDS
city: Perugia
country: Italy
facility: Azienda Ospedaliera Di Perugia
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Pozzilli
country: Italy
facility: Istituto Neurologico Mediterraneo Neuromed
city: Roma
country: Italy
facility: Fondazione PTV Policlinico Tor Vergata
city: Roma
country: Italy
facility: Ospedale San Giovanni Battista - ACISMOM
city: Roma
country: Italy
facility: IRCCS San Raffaele Pisana
city: Salerno
country: Italy
facility: Azienda Ospedaliera Universitaria OO.RR. San Giovanni di Dio Ruggi d'Aragona
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebrón - PPDS
city: Burgos
country: Spain
facility: C.A.U de Burgos - Hospital Universitario de Burgos
city: Cadiz
country: Spain
facility: Hospital Puerta del Mar
city: Donostia
country: Spain
facility: Hospital Universitario de Donostia
city: Madrid
country: Spain
facility: Hospital Universitario de La Princesa
city: Madrid
country: Spain
facility: Hospital Universitario La Paz - PPDS
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda
city: Móstoles
country: Spain
facility: Hospital HM Puerta del Sur
city: Pamplona
country: Spain
facility: Clinica Universidad Navarra
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
affiliation: Zambon SpA
name: Charlotte Keywood, MD
role: STUDY_DIRECTOR
References: