• To evaluate the long-term safety and tolerability of oral administration of 2 dosage levels of KNS 760704 in ALS patients (Part 2) [ Time Frame: 76 weeks ] [ Designated as safety issue: Yes ]
• To evaluate the effects of KNS-760704 on measures of clinical function [ Time Frame: 12 weeks and 76 weeks ] [ Designated as safety issue: Yes ]
• To evaluate the reliability and clinical predictive value of upright and supine vital capacity [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• To evaluate the effects of KNS-760704 on selected protein levels in blood and cerebrospinal fluid [ Time Frame: 12 weeks and 28 weeks ] [ Designated as safety issue: No ]

• To evaluate the safety and tolerability of oral administration of 2 dosage levels of KNS-760704 for 28 weeks in ALS patients (Part 2) [ Time Frame: 28 weeks ] [ Designated as safety issue: Yes ]
• To evaluate the effects of KNS-760704 on measures of clinical function [ Time Frame: 12 weeks and 28 weeks ] [ Designated as safety issue: Yes ]
• To evaluate the reliability and clinical predictive value of upright and supine vital capacity [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• To evaluate the effects of KNS-760704 on selected protein levels in blood and cerebrospinal fluid [ Time Frame: 12 weeks and 28 weeks ] [ Designated as safety issue: No ]

This is a 2-part study of KNS-760704 in patients with ALS.

• Part 1 is a randomized, placebo-controlled, multi-center study to evaluate the safety, tolerability, and clinical effects of oral administration of 3 dosage levels of KNS 760704 vs. placebo for 12 weeks.
• Part 2 is a randomized, double-blind, 2-arm, parallel group, extension study evaluating the safety, tolerability, and clinical effects of oral administration of 2 dosage levels of KNS-760704 for up to 76 weeks.

This is a double-blind, randomized, placebo-controlled study evaluating the safety and efficacy of KNS-760704 compared to placebo. The study will be conducted in 2 parts.

In Part 1, approximately 80 eligible patients will be randomized to 1 of 4 treatment groups for 12 weeks of treatment: placebo; low-dose; mid-dose; or high-dose KNS-760704. Participants meeting eligibility requirements will be enrolled at approximately 20 centers in the U.S. In addition to the visit to determine eligibility and the first visit to take study drug, participants will be required to make 5 additional research clinic visits in Part 1.

Participants who complete all 12 weeks of Part 1 will be eligible for randomization to Part 2. The duration of Part 2 of the study is 76 weeks. Subjects will receive 1 of 2 active treatment groups for 72 weeks (low-dose or high-dose KNS-760704) and placebo for the remaining 4-week period in Part 2. Participants will not be told when the 4 weeks of placebo treatment will be given. During Part 2, participants will be required to make 12 research clinic visits, including the baseline visit.

• Placebo Comparator: placebo treatment Q12H
• Experimental: low-dose KNS-760704
• Experimental: mid-dose KNS-760704
• Experimental: high-dose KNS-760704

Inclusion Criteria:

• Patients with diagnosis of familial or sporadic ALS, defined as meeting the possible, laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS according to the World Federation of Neurology El Escorial criteria
• Patients with ALS symptom onset < 24 months from randomization
• Patients with upright VC > 65% of predicted for age, height, and gender

Exclusion Criteria:

• Patients in whom causes of neuromuscular weakness other than ALS have not been excluded
• Patients without clinical evidence of upper motor neuron dysfunction
• Patients with clinically suspected ALS according to the World Federation of Neurology El Escorial criteria
• Patients with prior exposure to KNS-760704 or the R(+) enantiomer of pramipexole (i.e., R(+)-pramipexole)
• Patients taking other investigational agents (including lithium) within 30 days of randomization or during the study