Effect of Safinamide on Parkinson's Disease Related Chronic Pain

Idiopathic Parkinson Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03841604
• Other study ID #: Z7219M01
• Secondary ID: 2017-002426-20
• Status: Completed
• Phase: Phase 4
• Start date: April 9, 2019
• Est. completion date: May 3, 2021

Study information

• Verified date: May 2020
• Source: Zambon SpA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 94
• Est. completion date: May 3, 2021
• Est. primary completion date: April 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Pain
• Idiopathic Parkinson Disease
• Parkinson Disease

Intervention

Drug:
• Safinamide Methanesulfonate
50 mg, 100 mg

Other:
• Safinamide methanesulfonate matching placebo
50 mg, 100 mg

Locations

Country	Name	City	State
Austria	Medizinische Universitat Innsbruck	Innsbruck
Austria	Institut für Neuroimmunologische und Neurodegenerative Erkrankungen	Wien
France	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
Germany	St. Joseph Krankenhaus Berlin	Berlin
Germany	Universitätsklinikum Carl Gustav Carus an der TU Dresden	Dresde
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
Italy	Zambon Investigative Site	Chieti
Italy	Centro per la Malattia di Parkinson e i Disturbi del Movimento	Milano
Italy	Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico	Milano
Italy	Ospedale San Raffaele S.r.l. - PPDS	Milano
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	IRCCS San Raffaele Pisana	Roma
Italy	Ospedale San Giovanni Battista - ACISMOM	Roma
Italy	Azienda Ospedaliera Universitaria OO.RR. San Giovanni di Dio Ruggi d'Aragona	Salerno
Spain	Hospital de La Santa Creu i Sant Pau	Barcelona
Spain	Hospital del Mar	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
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 del Rocio	Sevilla
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
Spain	Hospital Universitario Miguel Servet	Zaragoza

Sponsors (1)

Lead Sponsor	Collaborator
Zambon SpA

Countries where clinical trial is conducted

Austria,  France,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Number of Subjects With a Reduction of =2 Points in Pain Severity at Week 16, Compared to Baseline	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.	Week 16
Secondary	The Change From Baseline to Week 16 in the Clinical Global Impression of Change (CGI-C) Score for Pain	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": = substantial improvement; = moderate improvement; = minimum improvement; = No change; = Minimum worsening; = moderate worsening; = substantial worsening. of course the higher the score, the worse the outcome.	Baseline and Week 16
Secondary	The Global Impression of Severity (CGI-S) Score for Pain at Week 16	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: = normal, not at all ill; = borderline mentally ill; = mildly ill; = moderately ill; = markedly ill; = severely ill; = among the most severely ill patients. of course the higher the score, the worse the outcome.	Baseline and Week 16
Secondary	The Change From Baseline to Week 16 in the Patient Global Impression of Change (PGI-C) Score for Pain	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: = no change (or condition has got worse); = almost the same, hardly any change at all; = a little better, but not noticeable change; = somewhat better, but the change has not made any real difference; = moderately better, and a slight but noticeable change; = better and a definite improvement that has made a real and worthwhile difference; = a great deal better, and a considerable improvement that has made all the difference.; Of course, the higher the score, the better the outcome.	Baseline and Week 16
Secondary	Number of Subjects With Concomitant Use of Pain Drugs at Different Timepoints	This outcome describes the number of subjects which had concomitant assumption of pain drugs at different timepoints.	Baseline, weeks 4, 8 and 16
Secondary	Amount of PRN PD Pain Medication: Count of Subjects Who Used PRN PD Pain Medication in the 7 Days Preceding Visits	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: as the number of subjects who were taking pain medication in the 7 days preceding visits at different timepoints; in the number of days on which PRN PD pain medication was taken at different timepoints.	at Baseline and weeks 4, 8 and 16
Secondary	Amount of PRN PD Pain Medication: Number of Days on Which PRN PD Pain Medication Was Taken at Different Timepoints	The analysis of amount of concomitant PRN PD pain medications as reported in the subject diary was summarized: as the number of days on which PRN PD pain medication was taken at different timepoints.; as the number of subjects who were taking pain medication in the 7 days preceding visits at different timepoints.	At Baseline and weeks 4, 8 and 16
Secondary	Change From Baseline to Week 16 in the Hospital Anxiety and Depression Scale (HADS) Score	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
Secondary	The Change From Baseline to Week 16 in MDS-UPDRS	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.	Baseline and Week 16