Ibudilast (MN-166) in Subjects With Amyotrophic Lateral Sclerosis (ALS)

Inclusion Criteria:

- Written informed consent is obtained and willing and able to comply with the protocol
in the opinion of the Investigator.

- Male or female subjects ages ≥ 18 to 80 years, inclusive

- Diagnosis of familial or sporadic ALS as defined by the El Escorial-Revised (2000)
research diagnostic criteria for ALS [Clinically Definite, Clinically Probable,
Probable-Laboratory-Supported]

- Diagnosis of ALS with onset of less than or equal to 5 years from first clinical
weakness

- Slow vital capacity ≥ 60% of predicted within 1 month prior to Treatment Day 1

- Currently on a stable dose of riluzole for at least 30 days prior to initiation of
study drug. Subjects not currently taking riluzole will be started on 50 mg qd for the
first 7 days followed by 50 mg bid for the following 21 days prior to screening.
Patients may be screened during this time period but not started on study drug until
they are on a stable dose of riluzole.

- All females will be considered to be of childbearing potential unless they are
postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age
group, and without other known or suspected cause) or have been sterilized surgically
(i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all
with surgery at least 1 month before dosing). Females of childbearing potential must
use an effective method of contraception throughout the entire study period and for 30
days after study drug discontinuation.

- Females must not be lactating or pregnant at Screening or Baseline (as documented by a
negative beta-human chorionic gonadotropin [ß-hCG] (or human chorionic gonadotropin
[hCG]). A separate baseline assessment is required if a negative screening pregnancy
test was obtained more than 72 hours before the first dose of study drug.

- Males should practice contraception as follows: condom use and contraception by female
partner.

- Able to swallow study medication capsules.

- Subject is willing and able to comply with the protocol assessments and visits, in the
opinion of the study nurse/coordinator and the Investigator.

- Has no known allergies to the study drug or its excipients.

- Has received 23-valent pneumococcal vaccine within 4 years prior to starting clinical
trial.

Exclusion Criteria:

- Use of tracheostomy, tracheostomy invasive mechanical ventilation [TIMV].

- Greater than 3% predicted loss in post-diagnosis vital capacity per month or a greater
than 1 unit loss in post diagnosis ALSFRS-R total score per month [ exclusive of loss
due to beginning use of assistive devices]

- Confirmed hepatic insufficiency or abnormal liver function (AST and/or ALT greater
than 3 times the upper limit of the normal range)

- Renal insufficiency as defined by a serum creatinine greater than 1.5 times the upper
limit of normal range

- Currently has a clinically significant psychiatric disorder or dementia which would
preclude evaluation of symptoms.

- Has a clinically significant medical condition (other than ALS) including the
following: neurological, metabolic, hepatic, renal, hematological, pulmonary,
cardiovascular, gastrointestinal, urological disorder, or central nervous system
infection that would pose a risk to the subject if they were to participate in the
study or that might confound the results of the study.

- History of malignancy < 5 years prior to signing the informed consent, except for
adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.

- ECG finding of QTcB prolongation > 450 ms for males and > 470 ms for females at
screening

- History of HIV (human immunodeficiency virus), clinically significant chronic
hepatitis, or other active infection

- Subject has a history of stomach or intestinal surgery or any other condition that
could interfere with or is judged by the Investigator to interfere with absorption,
distribution, metabolism, or excretion of study drug.

- Subject has a history of alcohol or substance abuse (DSM-IV-TR criteria) within 3
months prior to screening or alcohol or substance dependence (DSM-IV-TR criteria)
within 12 months prior to screening.

- Subject has poor peripheral venous access that will limit the ability to draw blood as
judged by the Investigator.

- Currently participating, or has participated in, a study with an investigational or
marketed compound or device within 3 months prior to signing the informed consent.

- Unable to cooperate with any study procedures, unlikely to adhere to the study
procedures and keep appointments, in the opinion of the Investigator.

Advanced ALS group will follow the same inclusion/exclusion as the early ALS subjects with
the exception of the following:

Inclusion criteria:

- Diagnosis of ALS with onset of ≤10 years from first clinical weakness

- On Non-invasive ventilator with Non-invasive pressure [P-NIV] or volume [V-NIV] cycled
ventilation stable use for ≥ 4 hours daily for 1 month prior to Treatment Day.

- Slow vital capacity ≥ 20% of predicted (Knudsen 1983) within 1 month prior to
Treatment Day 1

- Able to swallow study medication capsules or have gastrostomy tube access for delivery
of contents of medication capsule.

Exclusion criteria:

- Use of tracheostomy, tracheostomy invasive mechanical ventilation [TIMV].

- No rate of progression exclusion.