Study to Assess Safety, Tolerability and MTD of a Central Pattern Generator-activating Tritherapy (SPINALON) in Patients With Chronic Spinal Cord Injury

Nordic Life Science Pipeline Inc.

Status and phase: Completed; Phase 2; Phase 1

Conditions: Spinal Cord Injury

Treatments: Drug: SPINALON (buspirone + levodopa + cardidopa)

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT01484184

SPIN-01

Details and patient eligibility

About

As a first-in-class (Central Pattern Generator or CPG activator) approach, this tritherapy candidate called SPINALON has been identified and is currently under development for its capacity to temporarily induce episodes of involuntary locomotor movements. The primary objective of this Phase I/IIa study is to assess safety and tolerability of a single escalating dose of SPINALON (levodopa + carbidopa + buspirone) in chronic spinal cord-injured patients. As a secondary objective, preliminary evidence of efficacy will also be sought.

Full description

Spinal cord injury (SCI) is generally considered as an irreversible condition for which no curative treatment has yet been found. A recent study sponsored by the Christopher & Dana Reeve Foundation revealed an incidence ranging between 40 and 60 cases per million population and a prevalence estimated to be several times greater (new data: 1,275,000 cases) than previously reported(previous data: 200,000 cases).

SPINALON (levodopa + carbidopa + buspirone) was discovered by Dr. Guertin and colleagues as a drug treatment candidate that can acutely elicit temporarily (lasting approximately 30-60 minutes) episodes of CPG activity and corresponding powerful weight-bearing hindlimb stepping in completely SCI subjects (preclinical efficacy data obtained from mice and turtles completely spinal cord transected thoracically).

As such, SPINALON is currently being developed to become a chronic treatment (physical activity-based approach driven pharmacologically) against the multiple health problems or so-called 'secondary complications' associated specifically with the lack of physical activity (sarcopenia, osteoporosis, cardiovascular problems, dyslipidemia, obesity, type II diabetes, anemia, immune system deficiency, deep vein cloth, depression, etc.).

This study is a randomized, placebo-controlled, double-blind, single dose escalation study with fifty-one (51) patients who will receive either placebo capsules(starch) or capsules with buspirone only, levodopa/carbidopa only or buspirone/levodopa/carbidopa (SPINALON).

Enrollment: 50 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Clinical diagnosis of complete or motor-complete SCI (ASIA-A, ASIA-B)
• Chronically injured (at least 3 months post-injury)
• Paraplegic (within T1-T12) or tetraplegic (within C3-C8)
• In relatively good health condition (no significant bed sore, urinary tract infection)
• 18-65 years of age
• Men and women
• Quebec Province residents only

Exclusion criteria

• With unclear diagnosis
• Displayed a form of involuntary rhythmic leg muscle activity (restless leg syndrome, spontaneous activity in supine position, etc.) in the last 3 months prior to this study.
• Acute or subacute stage (within 1 day and 3 months post-injury)
• Non-traumatic (e.g., multiple sclerosis, syringomyelia, spinal tumor,etc.)
• Are given monoamine oxidase (MAO) inhibitors (two weeks prior and after Spinalon administration)
• Had seizures
• Had tumor(s) (malignant or non-malignant) or in situ carcinoma in the last five (5) years
• Allergic or hypersensitive to buspirone, levodopa or carbidopa
• Can not take sympathomimetic amines (e.g., epinephrine, pseudoephedrine)
• Currently suffering of heart problems, blood related diseases, endocrine disease, liver disease, lung disease, or kidney disease
• Receiving antihypertensive drugs
• Receiving tricyclic antidepressant
• Receiving dopamine D2 receptor antagonists (e.g., phenothiazines, butyrophenones, risperidone)
• Receiving phenytoin and papaverine
• With glaucoma
• With psychiatric or mental disorder(s)
• Had gastrointestinal ulcer(s) in the last five (5) years
• Pregnant or lactating woman (all women between 18 and 50 year-old not yet confirmed as pregnant, will be tested (urine test - TestPak Plus, Abbott Laboratories) on medical exam-day due to the teratogenic potential of levodopa/carbidopa.
• Children (younger than 18 year-old) or elderly (older than 65 year-old)
• Not resident of Quebec Province

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Double Blind

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50 participants in 2 patient groups, including a placebo group

buspirone or levodopa/carbidopa

Active Comparator group

Description:

Another 2-arm design will be tested composed of 16 subjects receiving drug A or drug B at MTD dose of the combined study drug as identified in the previous 2-arm groups.

Treatment:

Drug: SPINALON (buspirone + levodopa + cardidopa)

Placebo

Placebo Comparator group

Description:

First, a 2-arm design will be used, the first arm being composed of 3 subjects receiving the lowest dose of SPINALON, the second arm being composed of 1 subject receiving a placebo. This 2-arm design will be repeated consecutively with increasing doses, as long as the dose is well tolerated. Six (6) groups are expected to be tested with this 2-arm design.

Treatment:

Drug: SPINALON (buspirone + levodopa + cardidopa)