Study of Rasagiline in Patients With Amyotrophic Lateral Sclerosis

• ClinicalTrials.gov Identifier: NCT01879241
• Recruitment Status: Completed
• First Posted: June 17, 2013
• Last Update Posted: October 25, 2016
• Sponsor: University of Ulm
• Information provided by (Responsible Party): Albert Christian Ludolph, Prof., University of Ulm

Tracking Information

• First Submitted Date: June 12, 2013
• First Posted Date: June 17, 2013
• Last Update Posted Date: October 25, 2016
• Study Start Date: June 2013
• Actual Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 12, 2013): Survival in ALS-Patients with Rasagiline compared to placebo [ Time Frame: 18 Months ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 12, 2013)

• Change of total score of ALS Functional Rating Scale - Revised (ALSFRS-R) [ Time Frame: 18 Months ]
• Change of individual Quality of Life (SEIQoL, Schedule for the Evaluation of Individual Quality of Life [ Time Frame: 18 Months ]
• Change of slow vital capacity [ Time Frame: 18 Months ]

• 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: Study of Rasagiline in Patients With Amyotrophic Lateral Sclerosis
• Official Title: Efficacy, Safety and Tolerability Study of 1 mg Rasagiline in Patients With Amyotrophic Lateral Sclerosis (ALS) Receiving Standard Therapy (Riluzole) - An AMG Trial With a Market Authorized Substance

Brief Summary

The primary objective of the trial is to investigate the survival time (the time from randomization until death or end of the trial) compared between control group and experimental group.

This is a prospective, multicenter, randomized, stratified, parallel-group, double-blind trial comparing placebo with 1 mg/d rasagiline as add-on therapy to 100 mg riluzole in amyotrophic lateral sclerosis (ALS) in 250 enrolled patients. For entry, the El Escorial Criteria for the diagnosis of ALS will be used. The patients have to be stable on riluzole at least 4 weeks prior to randomization.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Amyotrophic Lateral Sclerosis

Intervention

• Drug: Rasagiline
• Drug: Placebo
  a sugar pill manufactured to mimic Rasagiline 1 mg tablet

Study Arms

• Experimental: Rasagiline

  Rasagiline

  1 mg/day; 18 months

  Intervention: Drug: Rasagiline
• Placebo Comparator: Placebo
  once daily, 18 months
  Intervention: Drug: Placebo

Publications *

• Waibel S, Reuter A, Malessa S, Blaugrund E, Ludolph AC. Rasagiline alone and in combination with riluzole prolongs survival in an ALS mouse model. J Neurol. 2004 Sep;251(9):1080-4. doi: 10.1007/s00415-004-0481-5.
• Ludolph AC, Schuster J, Dorst J, Dupuis L, Dreyhaupt J, Weishaupt JH, Kassubek J, Weiland U, Petri S, Meyer T, Grosskreutz J, Schrank B, Boentert M, Emmer A, Hermann A, Zeller D, Prudlo J, Winkler AS, Grehl T, Heneka MT, Wollebaek Johannesen S, Goricke B; RAS-ALS Study Group. Safety and efficacy of rasagiline as an add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: a randomised, double-blind, parallel-group, placebo-controlled, phase 2 trial. Lancet Neurol. 2018 Aug;17(8):681-688. doi: 10.1016/S1474-4422(18)30176-5. Epub 2018 Jun 19.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 24, 2016): 252
• Original Estimated Enrollment (submitted: June 12, 2013): 250
• Actual Study Completion Date: August 2016
• Actual Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Possible, probable (clinically or laboratory) or definite ALS according to the revised version of the El Escorial World Federation of Neurology criteria
• Disease duration more than 6 months and less than 3 years (inclusive). Disease onset defined as date of first muscle weakness, excluding fasciculations and cramps
• Vital capacity more than 50% of normal (slow vital capacity; best of three measurements)
• Age: ≥ 18 years
• Continuously treated with 100 mg riluzole for at least four weeks
• Capable of thoroughly understanding all information given and giving full informed consent according to GCP
• Women of childbearing age must be non-lactating and surgically sterile or using a highly effective method of birth control and have a negative pregnancy test. Acceptable methods of birth control with a low failure rate i.e. less than 1% per year) when used consistently and correct are such as implants, injectables, combined oral contraceptives, hormonal intrauterine devices (IUDs), or double-barrier methods (condom or diaphragm with spermicidal agent or IUD), sexual abstinence or vasectomized partner

Exclusion Criteria:

• Previous participation in another clinical study within the preceding 12 weeks
• Tracheostomy or assisted ventilation of any type during the preceding three months
• Gastrostomy
• Any medical condition known to have an association with motor neuron dysfunction which might confound or obscure the diagnosis of ALS
• Presence of any concomitant life-threatening disease or impairment likely to interfere with functional assessment
• Patients on sympathomimetic agents. This includes pseudoephedrine, phenylephrine, phenylpropanolamine, and ephedrine.
• Patients on analgesics with serotoninergic properties such as meperidine, tramadol, methadone and propoxyphene.
• Patients on serotonin reuptake inhibitors (SSRIs). This includes fluoxetine or fluvoxamine.
• Patients on dextromethorphan, St. John's wort, cyclobenzaprine or other MAO inhibitors (selective or non-selective)
• Patients taking Antidepressants
• Confirmed hepatic insufficiency or abnormal liver function (ASAT and/or ALAT greater than 3 times the upper limit of the normal range)
• Renal insufficiency (serum creatinine more than 2.26 mg/dL)
• Evidence of major psychiatric disorder or clinically evident dementia precluding evaluation of symptoms
• Known hypersensitivity to any component of the study drug
• Liable to be not cooperative or comply with the trial requirements (as assessed by the investigator), or unable to be reached in the case of emergency
• Female with childbearing potential, if no adequate contraceptive measures are used
• Pregnancy or breast-feeding females

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT01879241
• Other Study ID Numbers: RAS-ALS; 2011-004482-32 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Albert Christian Ludolph, Prof., University of Ulm
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Ulm
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Albert C. Ludolph, MD, Prof.; Department of Neurology, University of Ulm

• PRS Account: University of Ulm
• Verification Date: October 2016