Safinamide in Idiopathic Parkinson's Disease (IPD) With Motor Fluctuations, as add-on to Levodopa (SETTLE)

• ClinicalTrials.gov Identifier: NCT00627640
• Recruitment Status: Completed
• First Posted: March 3, 2008
• Last Update Posted: March 29, 2013
• Sponsor: Newron Pharmaceuticals SPA
• Information provided by (Responsible Party): Newron Pharmaceuticals SPA

Tracking Information

• First Submitted Date: February 13, 2008
• First Posted Date: March 3, 2008
• Last Update Posted Date: March 29, 2013
• Study Start Date: February 2009
• Actual Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 29, 2008): Evaluate the change from baseline to W24 in daily "on" time ("on" time without dyskinesia plus "on" time with minor dyskinesia) [ Time Frame: 24 weeks ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: February 29, 2008): Evaluate the changes from baseline to W24 in Activities of Daily Living, cognition, dyskinesias, change in global clinical status, motor symptoms, motor fluctuations, change in levopoda dose and Health Related Quality of life [ Time Frame: 24 weeks ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safinamide in Idiopathic Parkinson's Disease (IPD) With Motor Fluctuations, as add-on to Levodopa
• Official Title: A Phase III, Double-blind, Placebo-controlled, Randomised Trial to Determine the Efficacy and Safety of a Dose Range of 50 to 100 mg/Day of Safinamide, as add-on Therapy, in Subjects With Idiopathic Parkinson's Disease With Motor Fluctuations, Treated With a Stable Dose of Levodopa and Who May be Receiving Concomitant Treatment With Stable Doses of a Dopamine Agonist, an Anticholinergic and/or Amantadine

Brief Summary

Parkinson's Disease is a major neurodegenerative disorder in which there is a progressive loss of dopamine-containing neurons. The understanding that PD is a syndrome of dopamine (DA) deficiency led to the introduction in the clinical practice of L-dopa, a precursor of DA that crosses the blood brain barrier, and also to the use of selective inhibitors of MAO-B, the major DA metabolising enzyme in man.

Safinamide is an inhibitor of MAO-B. This is a phase III trial to evaluate the efficacy and safety of safinamide (50 and 100 mg p.o. q.a.m.) compared to placebo as add-on therapy to a stable dose to levodopa in subjects with advance idiopathic Parkinson's Disease.

The principal efficacy measure is the increase in mean daily "on" time during the 18-hr diary recording period.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Idiopathic Parkinson's Disease

Intervention

• Drug: Safinimide 50-100 mg/day
  Safinamide, (S)-(+)-2-[4-(3-fluorobenzyloxy) benzylamino] propanamide methanesulfonate, is an a-aminoamide derivative
• Drug: Matching Placebo
  Matching Placebo

Study Arms

• Experimental: 1
  1 active (50 - 100 mg/day)
  Intervention: Drug: Safinimide 50-100 mg/day
• Placebo Comparator: 2
  Intervention: Drug: Matching Placebo

• Publications *: Schapira AH, Fox SH, Hauser RA, Jankovic J, Jost WH, Kenney C, Kulisevsky J, Pahwa R, Poewe W, Anand R. Assessment of Safety and Efficacy of Safinamide as a Levodopa Adjunct in Patients With Parkinson Disease and Motor Fluctuations: A Randomized Clinical Trial. JAMA Neurol. 2017 Feb 1;74(2):216-224. doi: 10.1001/jamaneurol.2016.4467.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 5, 2012): 549
• Original Estimated Enrollment (submitted: February 29, 2008): 484
• Actual Study Completion Date: March 2012
• Actual Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Male and female between the ages of 30 to 80 years with diagnosis of idiopathic Parkinson's Disease of more than 5 years duration, with a Hoehn and Yahr stage of I-IV during an "off" phase.

Be levodopa-responsive and have been receiving treatment with a stable dose of levodopa for at least 4 weeks.

Have motor fluctuations, with >1.5 hours "off" time during the day. Be able to maintain an accurate and complete diary (18-hour)

Exclusion Criteria:

Patients with medical conditions and/or taking concomitant medications that would have put them at risk, interfered with the study evaluations, or made them unable to complete the requirements of the study;.

Be in a late stage of Parkinson's Disease, and experiencing severe, disabling peak-dose or biphasic dyskinesia and/or unpredictable or widely swinging fluctuations in their symptoms.

Current diagnosis of substance abuse or history of alcohol or drug abuse in the past 3 months.

Have received treatment with safinamide previously. History of, or current depression psychosis (e.g. schizophrenia or psychotic depression) Evidence of dementia or cognitive dysfunction. History of allergic response to anticonvulsants, levodopa, or other anti-Parkinsonian agents.

Hypersensitivity or contraindications to MAO-B inhibitors. Ophthalmologic history including any of the following conditions: albino subjects, family history of hereditary retinal disease, progressive and/or severe diminution of visual acuity (i.e., 20/70), retinitis pigmentosa, retinal pigmentation due to any cause, any active retinopathy or ocular inflammation (uveitis), or diabetic retinopathy.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 30 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Canada, Estonia, France, Germany, Hungary, India, Israel, Korea, Republic of, Malaysia, Netherlands, New Zealand, Slovakia, Spain, Switzerland, Taiwan, Thailand, United Kingdom, United States

Administrative Information

• NCT Number: NCT00627640
• Other Study ID Numbers: 27919; IND: 63,901; EudraCT Number: 2007-002964-90
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Newron Pharmaceuticals SPA
• Original Responsible Party: David Weiner, MD, Senior Medical Director, EMD Serono, Inc.
• Current Study Sponsor: Newron Pharmaceuticals SPA
• Original Study Sponsor: EMD Serono
• Collaborators: Not Provided

Investigators

• Study Director: Algirdas Kakarieka, MD; Merck Serono S.A., Geneva

• PRS Account: Newron Pharmaceuticals SPA
• Verification Date: June 2012