Rasagiline in Subjects With Amyotrophic Lateral Sclerosis (ALS)

The study is a phase II, double-blind, placebo-controlled, multicenter study of rasagiline 2mg/day. Subjects will be assigned to either active agent or placebo (3:1) for twelve months. Subjects will undergo outpatient evaluations at screening, baseline, and months 1, 2, 4, 6, 8, 10 and 12 and telephone assessments at months 3, 5, 7 and 9. There will be a close-out phone call 30 days post month 12.

Inclusion criteria

• A clinical diagnosis of laboratory-supported probable, probable, or definite ALS, according to a modified El Escorial criteria, by the study investigator (Appendix IV).
• 21 to 80 years of age inclusive.
• VC greater or equal to 75% of predicted at screening and baseline.
• Onset of weakness within 2 years prior to enrollment.
• If patients are taking riluzole for ALS, they must be on a stable dose for at least thirty days prior to the baseline visit.
• Women of childbearing age must be non-lactating and surgically sterile or using an effective method of birth control and have a negative pregnancy test.
• Willing and able to give signed informed consent that has been approved by the Institutional Review Board (IRB).

Exclusion criteria

• Requirement for tracheotomy ventilation or non-invasive ventilation for > 23 hours per day.
• Patients on sympathomimetic agents. This includes pseudoephedrine, phenylephrine, phenylpropanolamine, and ephedrine.
• Patients on analgesics with serotoninergic properties such as meperidine, tramadol, methadone and propoxyphene, flexeril.
• Patients on fluoxetine or fluvoxamine.
• Patients taking amitriptyline > 50 mg/d, trazodone and sertraline > 100 mg/d, citalopram > 20 mg/d or paroxetine > 30 mg/d.
• Diagnosis of other neurodegenerative diseases (Parkinson disease, Alzheimer disease, etc).
• Clinically significant history of unstable medical illness (unstable angina, advanced cancer, etc) over the last 30 days.
• Has a diaphragm pacing device or plan on obtaining a diaphragm pacing device during the course of the study.
• History of renal disease.
• History of liver disease.
• Current pregnancy or lactation.
• Limited mental capacity such that the patient cannot provide written informed consent or comply with evaluation procedures.
• History of recent alcohol or drug abuse or noncompliance with treatment or other experimental protocols.
• Vital Capacity (VC) < 75% of predicted.
• Receipt of any investigational drug within the past 30 days.
• Women with the potential to become pregnant who are not practicing effective birth control.
• Poorly controlled hypertensive subjects or resting systolic blood pressure (SBP) > 160 mmHg and/or diastolic (DBP) > 95 mmHg.
• Use of BiPAP at screening.