Effect of Safinamide on Parkinson's Disease Related Chronic Pain

• Sponsor: Zambon SpA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03841604
• Collaborator: (none)
• Enrollment: 71
• Locations: 45
• Arms: 2
• Actual Duration (Months): 24.8
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a Phase IV, international, multicentre, randomised, double-blind, placebo controlled study in IPD patients, experiencing motor fluctuations and PD related chronic pain while on stable doses of levodopa (L-Dopa).

Participants will be randomized 2:1 to receive either active or placebo

Condition or Disease	Intervention/Treatment	Phase
Idiopathic Parkinson Disease	Drug: Safinamide Methanesulfonate; Drug: Safinamide methanesulfonate matching placebo	Phase 4

Detailed Description

This is an international, multicentre, randomised, double-blind, placebo-controlled study.

Patients will be randomized 2:1 to receive either active and placebo Approximately 132 participants will be screened, of which 105 will be enrolled Study participation will be up to a maximum duration of 19 weeks and will comprise a screening period (1 to 2 weeks) and a treatment period (16 weeks). A telephone follow-up call will be performed 1 week after the end of treatment

Study Design

• Study Type: Interventional
• Actual Enrollment: 71 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Apr 9, 2019
• Actual Primary Completion Date: Apr 30, 2021
• Actual Study Completion Date: May 3, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental Safinamide methanesulfonate film coated tablets once daily	Drug: Safinamide Methanesulfonate; 50 mg, 100 mg
Placebo Comparator: Placebo Safinamide methanesulfonate matching placebo film coated tablets once daily	Drug: Safinamide methanesulfonate matching placebo; 50 mg, 100 mg

Outcome Measures

Primary Outcome Measures

1. To evaluate the potential efficacy of safinamide 100 mg od, compared to placebo, as add-on therapy, for PD related chronic pain: Numerical Rating Scale (NRS) [16 weeks]

   Change in pain severity ("average worst pain experienced in the last 7 days"), as assessed by an 11-point Numerical Rating Scale (NRS). [0 point is the minimum and 10 point is the maximum. The higher the score, the more severe the pain]

Secondary Outcome Measures

1. Percentage of pain responders [16 weeks]

   Reduction in pain severity of ≥2 points ("average worst pain experienced in the last 7 days") as assessed by an 11-point NRS, compared to baseline [0 point is the minimum and 10 point is the maximum. The higher the score, the more severe the pain]

2. Clinical Global Impression for pain (change) [16 weeks]

   Change in the CGI-C (Clinical Global Impression - Change) score for pain [ a seven-point scale, it ranges from Very much Improved to Very much Worse]

3. Clinical Global Impression for pain (severity) [16 weeks]

   The CGI-S (Clinical Global Impression - Severity) score for pain at week 16 [ a seven-point scale, it ranges from Very much Better to Very much Worse]

4. Patient Global Impression for pain [16 weeks]

   Change in the PGI-C (Patient Global Impression - Change) score for pain [ a seven-point scale, it ranges from Very much Better to Very much Worse]

5. Reduction of pain drugs (Percentage) [16 weeks]

   Percentage of reduction in number of concomitant pain drugs

6. Reduction of pain drugs (amount) [16 weeks]

   Amount of PRN pain medication

7. Reduction of pain drugs [16 weeks]

   Number of patients with at least one intake of PRN pain medication.

8. Mood [16 weeks]

   Change in the Hospital Anxiety and Depression Scale (HADS) score [Fourteen item scale, seven items relate to anxiety and seven relate to depression. The anxiety and depression subscales each range from 0 to 21, with higher scores indicating higher anxiety/depression complains]

9. Motor and non-motor symptoms [16 weeks]

   Change in the MDS-UPDRS (total score and subscores) [The MDS-UPDRS has four parts: Part I (non-motor experiences of daily living), Part II (motor experiences of daily living, Part III (motor examination) and Part IV (motor complications)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 visitt.

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

1. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medizinische Universitat Innsbruck	Innsbruck		Austria	6020
2	Institut für Neuroimmunologische und Neurodegenerative Erkrankungen	Wien		Austria	1220
3	Hopital Gabriel Montpied	Clermont-Ferrand		France	63000
4	CHU de GRENOBLE	Grenoble		France	38700
5	Hopitaux de La Timone	Marseille		France	13385
6	Centre Hospitalier Universitaire de Nimes	Nîmes		France	30900
7	Hopital de Hautepierre	Strasbourg		France	67200
8	Hôpital Pierre-Paul Riquet	Toulouse		France	31300
9	St. Joseph Krankenhaus Berlin	Berlin		Germany	13088
10	Universitätsklinikum Carl Gustav Carus an der TU Dresden	Dresde		Germany	01307
11	Katholische Kliniken Ruhrhalbinsel GmbH	Essen		Germany	45257
12	Neurologische Praxis	Gera		Germany	07551
13	University Medicine Göttingen Germany	Göttingen		Germany	37075
14	Klinik Haag i. OB	Haag		Germany	83527
15	Universitätsklinikum Gießen und Marburg GmbH	Marburg		Germany	35043
16	Universitätsklinikum Münster	Münster		Germany	48149
17	NeuroPoint Akademie	Ulm		Germany	89073
18	Universitätsklinikum Ulm	Ulm		Germany	89081
19	Zambon Investigative Site	Chieti		Italy	66013
20	Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico	Milano		Italy	20122
21	Centro per la Malattia di Parkinson e i Disturbi del Movimento	Milano		Italy	20126
22	Ospedale San Raffaele S.r.l. - PPDS	Milano		Italy	20133
23	Azienda Ospedaliera Di Perugia	Perugia		Italy
24	Azienda Ospedaliero Universitaria Pisana	Pisa		Italy	56124
25	Istituto Neurologico Mediterraneo Neuromed	Pozzilli		Italy	86077
26	Fondazione PTV Policlinico Tor Vergata	Roma		Italy	00133
27	Ospedale San Giovanni Battista - ACISMOM	Roma		Italy	00148
28	IRCCS San Raffaele Pisana	Roma		Italy	00163
29	Azienda Ospedaliera Universitaria OO.RR. San Giovanni di Dio Ruggi d'Aragona	Salerno		Italy	84084
30	Hospital del Mar	Barcelona		Spain	08003
31	Hospital de La Santa Creu i Sant Pau	Barcelona		Spain	08025
32	Hospital Universitario Vall d'Hebrón - PPDS	Barcelona		Spain	08035
33	C.A.U de Burgos - Hospital Universitario de Burgos	Burgos		Spain	09006
34	Hospital Puerta del Mar	Cadiz		Spain	11009
35	Hospital Universitario de Donostia	Donostia		Spain	20014
36	Hospital Universitario de La Princesa	Madrid		Spain	28006
37	Hospital Universitario La Paz - PPDS	Madrid		Spain	28046
38	Hospital Universitario Puerta de Hierro - Majadahonda	Madrid		Spain	28222
39	Hospital HM Puerta del Sur	Móstoles		Spain	28938
40	Clinica Universidad Navarra	Pamplona		Spain	31008
41	Complejo Hospitalario de Navarra	Pamplona		Spain	31008
42	Hospital Universitario Virgen Macarena	Sevilla		Spain	41009
43	Hospital Universitario Virgen del Rocio	Sevilla		Spain	41013
44	Hospital Universitari i Politecnic La Fe de Valencia	Valencia		Spain	46026
45	Hospital Universitario Miguel Servet	Zaragoza		Spain	50009

Sponsors and Collaborators

• Zambon SpA

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Zambon SpA
• ClinicalTrials.gov Identifier: NCT03841604
• Other Study ID Numbers: Z7219M01
• First Posted: Feb 15, 2019
• Last Update Posted: May 19, 2021
• Last Verified: May 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Parkinson Disease; Chronic Pain

Study Results

No Results Posted as of May 19, 2021