Combination Therapy With Dalfampridine and Locomotor Training for Chronic, Motor Incomplete Spinal Cord Injury

Research suggests that combining therapies could result in important gains in restoring
function and improving quality of life in persons with spinal cord injury (SCI). Locomotor
training is an activity-dependent rehabilitation therapy that provides repetitive stepping
facilitated by manual assistance and body weight support on a treadmill. Recent studies
report improvements in walking and standing in individuals with motor incomplete SCI that
have undergone intensive standardized locomotor training therapy. Extended release
dalfampridine (also known as fampridine or 4-aminopyridine [4-AP]) is a broad spectrum
potassium channel blocker that has been shown in animal studies to increase conduction of
action potentials in demyelinated axons. Dalfampridine was recently approved by the U.S. Food
and Drug Administration (FDA) as a treatment to improve walking in persons with multiple
sclerosis (MS). Demyelination is also a prominent feature of incomplete SCI that contributes
to the clinical presentation of persons with these injuries.

The purpose of this study is to determine the efficacy, safety, and tolerability of treatment
with dalfampridine in combination with locomotor training in persons with chronic, motor
incomplete SCI. We hypothesize that persons undergoing combination therapy with dalfampridine
and locomotor training will show significantly greater improvements in walking speed and
other measures of SCI function than those receiving locomotor training alone.

Inclusion Criteria:

- Age 18 to 70 years, inclusive;

- Neurological impairment secondary to a traumatic spinal cord injury that occurred at
least twelve (12) months prior to the screening visit;

- Neurological level of the injury between C4 and T10, inclusive;

- The injury is classified as motor incomplete (AIS grade C or D);

- Able and willing to comply with the study protocol, including availability for all
scheduled clinic visits and locomotor training sessions.

Exclusion Criteria:

- The participant is a lactating female, or a female of childbearing potential who is
sexually active, has not had a hysterectomy or oophorectomy, and is not using an
approved birth control method (e.g. tubal ligation, implantable contraception device,
oral or injectable contraceptive, barrier method, or sexual activity restricted to
vasectomized partner);

- The participant has a history of seizures or treatment for seizure disorders;

- The participant has renal impairment (Creatinine Clearance < 80 mL/min);

- The participant has a known allergy to pyridine-containing substances or any of the
inactive ingredients of the dalfampridine;

- The participant has a clinically significant abnormal laboratory values or an abnormal
electrocardiogram (ECG);

- The participant has evidence of significant, diffuse, or generalized lower motor
neuron damage;

- The participant has received new concomitant medication less than 3 weeks before the
study or has a dose of current concomitant medication that is expected to change
during study;

- The participant has received botulinum toxin injection for spasticity within 4 months
of the screening visit;

- The participant has taken any other investigational drugs within 30 days before
screening;

- The participant is known to have been treated previously with dalfampridine (4
aminopyridine) in any formulation, whether through participation in a previous
fampridine study or by self-medication.

- The participant has received locomotor training therapy within 6 months of the
screening visit;

- The participant has a history of alcohol or drug abuse in the previous year;

- The participant has a medical condition that would interfere with interpretation of
study results or study conduct.

Note: Due to equipment and safety issues associated with locomotor training, participants
must weigh less than 300 lbs.