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

Phase 4

Terminated

• Conditions: Restless Leg Syndrome
• Interventions: Drug: Gabapentin immediate release; Drug: Gabapentin enacarbil extended release

• Registration Number: NCT02117076
• Lead Sponsor: Theresa Zesiewicz, MD

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.

Study Timeline

• Study Start: 2014-04
• Study First Submitted: 2014-04-15
• Study First Submitted QC: 2014-04-15
• Study First Posted: 2014-04-17
• Primary Completion: 2016-06
• Study Completion: 2016-06
• Status Verified: 2021-11
• Last Update Submitted: 2021-11-08
• Last Update Posted: 2021-11-16

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 5

Inclusion Criteria

1. Outpatients with a diagnosis of primary restless leg syndrome using the International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria8.
2. 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).
3. Age 18 years to 80 years.
4. International Restless Legs Scale (IRLS) Total severity score of ≥ 15 (moderate to severe severity). 8
5. Had significant sleep disturbance on item 4 of IRLS.8
6. Women of child-bearing potential must use a reliable method of contraception.
7. Informed consent. Subject must be willing and able to complete all study procedures.

Exclusion Criteria

1. Any illness that in the investigator's opinion preclude participation in this study.
2. Subjects with non-RLS-related sleep disorders (e.g., sleep apnea)
3. Subjects with neurological diseases or movement disorders other than RLS (e.g., diabetic neuropathy, Parkinson's disease, multiple sclerosis, dyskinesias, and dystonias)
4. Pregnancy or lactation.
5. Concurrent participation in another clinical study.
6. Dementia or other psychiatric illness that prevents the patient from giving informed consent (Mini-Mental State Examination scores less than 27).
7. Legal incapacity or limited legal capacity.
8. History of RLS symptom augmentation or early-morning rebound with previous dopamine-agonist treatment.
9. Clinically significant abnormalities in renal function. 3,8,10
10. Presence of severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease.
11. 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.
12. Body mass index greater than 34 kg/m2.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
gabapentin immediate release	Gabapentin immediate release	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.
gabapentin enacarbil extended release	Gabapentin enacarbil extended release	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.

Primary Outcome Measures

Name	Time	Method
International Restless Leg Syndrome Rating Scale (IRLS)	10 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Restless Leg Syndrome Quality of Life Scale (RLSQoL)	Baseline, day 35, day 54.	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.

Trial Locations

Locations (1)

University of South Florida; 🇺🇸 Tampa, Florida, United States