Effects of Gabapentin Enacarbil on Arousals, Heart Rate, Blood Pressure and PLMs in Restless Legs Syndrome

• Status: Unknown status
• Trial end date: 2016-07-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a phase IV single-blind, placebo run-in fixed dose single-group study to assess objective and subjective effects of GEn on sleep EEG, BP, and anterior tibialis EMG responsivity in patients with RLS. The study will include 8 visits over a period of up to 8 weeks for eligible subjects including a 1 to 3-week Screening/Washout Period, a 1-week placebo run-in period, and a 4-week Treatment Period.The first placebo dose will be administered within 1 to 3 weeks after Screening/Washout. The total duration of the study from the first subject enrolled to the last subject completed will be approximately 1 year.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Cleveland Sleep Research Center
• Collaborators: XenoPort, Inc.; YRT Limited
• Treatments: Gabapentin; gamma-Aminobutyric Acid

Criteria

Inclusion Criteria:

1. Male or female subjects ages 18 to 65 years with a diagnosis of primary moderate to severe RLS

2. A minimum of 6-month history of RLS symptoms

3. IRLS score >15 points (at visits 1 and 2) and a score of > 2 on item 4

4. RLS symptoms on at least 15 days during the month prior to screening (or if on treatment, similar symptom frequency before the start of treatment)

5. RLS symptoms for >4 out of 7 evenings /day during the week prior to screening

6. History of sleep disturbance due to RLS over the last 3 months

7. Subjective history of WASO ≥ 60 min; TST < 6.5 hours; subjective sleep latency ≥ 30 min on at least 3 nights per week within the last 3 months

8. Subjective complaint of WASO ≥ 60 min; TST< 6.5 hours; subjective sleep latency ≥ 30 min on at least 3 nights out of 7on the SSQ during the 1 week prior to Visit 2

9. Objective WASO of ≥30 minutes, TST < 6.5 hours and PLMI ≥ 10 during adaptation in baseline PSG 1

10. Females of child bearing potential willing to use birth control

11. Subject can read understand and sign consent form

12. Subject able to complete the study and to comply with study instructions and procedures

Exclusion Criteria:

1. Subject has an apnea-hypopnea index of ≥10/ hour during adaptation/baseline night PSGs. Subjects with OSA controlled by CPAP will be accepted

2. Evidence of secondary RLS

3. Subject has any of the following medical conditions, laboratory abnormalities or disorders:

Hepatic impairment Impaired renal function or renal dysfunction requiring hemodialysis; Serum ferritin level <20 mcg/L (ng/mL)

4. Clinically significant ECG abnormalities

5. Any unstable medical condition that could impact subject's safety and study outcomes

6. Uncontrolled hypertension at Screening or at time of treatment initiation

7. Subjects diagnosed with additional sleep disorders other than RLS-associated sleep disturbance

8. Neurologic disease or movement disorder, rheumatoid arthritis, fibromyalgia, uncontrolled psychiatric illness, current diagnosis or history of epilepsy or seizure disorder

9. Chronic hepatitis B or hepatitis C

10. Subject currently suffering from moderate or severe depression

11. Subject unable to discontinue prohibited medications during the Screening period and throughout the duration of the study.

12. Subject has consumed food or beverages containing more than 400 mg of caffeine or other xanthines (e.g., coffee, cola, tea, chocolate) per day over the preceding month prior to Screening or unwilling to refrain from consuming any caffeinated food or beverage within 8 hours prior to any PSG assessment.

13. Subject has typical consumption of >14 alcoholic units in any week, or more than 5 alcoholic units in any single day, over the month preceding the Screening visit or unwilling to refrain from consuming alcohol within 24 hours of any PSG assessment

14. Night workers, shift workers or any others whose sleeping habits are incompatible with the study design, or who would be required to make significant changes to their bedtime during the course of the study

15. Subject who might be non-compliant with the visit schedule, procedures, or medication administration

16. Subject is a pregnant or nursing female

17. A history of allergy or medically significant adverse reaction or intolerance to gabapentin or GEn

18. A history of alcohol, narcotic, benzodiazepine, or other substance abuse or dependence within the past year

19. A history of augmentation or early morning rebound of RLS symptoms without a history of prior response to treatment.

20. Subject has received previous treatment with levodopa/carbidopa, dopamine agonists, pregabalin, gabapentin or GEn in the 3 weeks prior to Visit

21. Subject has received' other treatments for RLS (e.g., opioids, benzodiazepines) at least 2 weeks prior to Visit 2

22. Participation in any clinical drug or device trial within 30 days prior to Baseline