Blinded, Randomized Study of Gabapentin (Neurontin®) and Gabapentin Enacarbil (Horizant™) in Restless Leg Syndrome

Study Overview
=================
Brief Summary
-----------------
The study will compare the safety, effectiveness and tolerability of gabapentin (Neurontin) versus gabapentin enacarbil (Horizant) as treatment restless leg syndrome.

Detailed Description
-----------------
The study will compare the safety, effectiveness and tolerability of gabapentin (Neurontin) versus gabapentin enacarbil (Horizant) as treatment restless leg syndrome. Subjects will be randomized to gabapentin (IR) or Horizant™ (ER). Dosing will be blinded to both patient and study team members. Once study medication dosing has been optimized, subjects will then remain on a stable dose for six weeks until study endpoint, after which subjects will be down-titrated off of study medications.

Official Title
-----------------
Blinded, Randomized Study of Gabapentin (Neurontin®) and Gabapentin Enacarbil (Horizant™) in Restless Leg Syndrome

Conditions
-----------------
Restless Leg Syndrome

Intervention / Treatment
-----------------
* Drug: Gabapentin immediate release
* Drug: Gabapentin enacarbil extended release


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Outpatients with a diagnosis of primary restless leg syndrome using the International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria8. RLS symptoms ≥ 15 nights of the month prior to study enrollment and for ≥ 4 of 7 consecutive nights in the week prior to study enrollment (if untreated). Age 18 years to 80 years. International Restless Legs Scale (IRLS) Total severity score of ≥ 15 (moderate to severe severity). 8 Had significant sleep disturbance on item 4 of IRLS.8 Women of child-bearing potential must use a reliable method of contraception. Informed consent. Subject must be willing and able to complete all study procedures. Exclusion Criteria: Any illness that in the investigator's opinion preclude participation in this study. Subjects with non-RLS-related sleep disorders (e.g., sleep apnea) Subjects with neurological diseases or movement disorders other than RLS (e.g., diabetic neuropathy, Parkinson's disease, multiple sclerosis, dyskinesias, and dystonias) Pregnancy or lactation. Concurrent participation in another clinical study. Dementia or other psychiatric illness that prevents the patient from giving informed consent (Mini-Mental State Examination scores less than 27). Legal incapacity or limited legal capacity. History of RLS symptom augmentation or early-morning rebound with previous dopamine-agonist treatment. Clinically significant abnormalities in renal function. 3,8,10 Presence of severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease. Concomitant treatment with drugs known to affect sleep/wake, RLS or periodic limb movements, including antidepressants. Subjects receiving treatment for RLS at screening will be required to discontinue and wash out for a minimum of 5 half-lives. Body mass index greater than 34 kg/m2.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: gabapentin immediate release<br>Gabapentin IR is the immediate release form of the medication. Subjects randomized to gabapentin IR will be started out at a dose of 300mg per day, taken one hour before bedtime for the first week. Daily dose will be increased by 300 mg daily every 4 days until 1200 mg of gabapentin IR is reached or until a stable, tolerated dose of gabapentin IR that relieves symptoms has been maintained for 2 weeks (IRLS scores less than 15). Those patients who cannot tolerate gabapentin IR will be allowed to down titrate by one dose level (300 mg daily), before dropping out of the study. | Drug: Gabapentin immediate release<br>* up to 1200 mg per day<br>* Other names: Neurontin;|
| Active Comparator: gabapentin enacarbil extended release<br>Horizant is the extended release form of gabapentin enacarbil. Subjects randomized to Horizant will take 600mg at 5 pm. After four days of stable dosing of Horizant, subjects in this study group will be evaluated by phone for changes in RLS symptoms and Patient Global Impression scale to determine if a dose increase is warranted. Subjects in this group may be titrated up to 1200 mg daily during the 2 week titration period. | Drug: Gabapentin enacarbil extended release<br>* up to 1200 mg per day<br>* Other names: Horizant;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| International Restless Leg Syndrome Rating Scale (IRLS) | The IRLS is a measure of severity of Restless Legs Syndrome. It includes 10 items, measured on a scale of 0-4. A score of 1-10 indicates mild severity, 11-20 indicates moderate severity, 21-30 is severe and 31-40 is very severe. Primary outcome is the difference in IRLS scores for each of the treatment regimens. from 0 to 4. | 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Restless Leg Syndrome Quality of Life Scale (RLSQoL) | The Restless Legs Syndrome Quality of Life questionnaire (RLSQoL) assesses the impact of RLS on daily life, emotional well-being, social life, and work life. | Baseline, day 35, day 54. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Restless leg syndrome, RLS, gabapentin, gabapentin enacarbil, Neurontin, Horizant