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

NCT02424695 | Unknown Phase 4

• 1 other identifier: XP-IIT-0031
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Restless Legs Syndrome

Keywords

Cortical arousal intensity; RLS; Heart rate; Blood pressure; PLMs

Outcome Measures

Primary Outcomes (1)

• The mean change from baseline to week 4 in intensity of cortical arousals associated with periodic limb movements (PLMs)

  Cortical EEG arousals will be scored using wavelet analysis of C3/A2 and C4/A1 EEG signals. Arousals scored in NREM sleep will be assigned a score from 0-9. This arousal scaling is entirely subjective. Wavelet analysis will be performed on each of the scaled arousals using wavelet features that correlate with arousal intensity. The arousal intensity will be measured using Wavelet Transform which is superior for analyzing signals such as EEG.

  4 weeks

Secondary Outcomes (14)

• The mean change from baseline to week 4 in heart rate variability associated with arousals secondary to periodic limb movements (PLMs)

  4 weeks

• The mean change from baseline to week 4 in blood pressure associated with arousals secondary to periodic limb movements (PLMs)

  4 weeks

• The mean change from baseline to week 4 in periodic limb movement (PLM) intensity

  4 weeks

• The mean change from Baseline to week 4 in Rechtschaffen and Kales polysomnography parameters

  4 weeks

• The mean change from baseline to week 4 in International Restless Legs Syndrome (IRLS) Rating Scale total score

  4 weeks

Study Arms (1)

Single Gabapentin Enacarbil Arm

EXPERIMENTAL

Gabapentin Enacarbil (Gen) 600 mg will be administered once daily for 4 weeks Matching placebo will be administered once daily for one week prior initiation of treatment with GEn

Drug: Gabapentin Enacarbil (GEn); Drug: Placebo

Interventions

Gabapentin Enacarbil (GEn) DRUG

HORIZANT Extended-Release Tablets containing 600 mg of gabapentin enacarbil are white to off-white, with occasional black/grey spots, oval-shaped tablets debossed with "GS LFG", supplied as: 600 mg: NDC 53451-0101-1.The drug will be stored at 25°C (77°F) (excursions permitted 15° to 30°C (59° to 86°F)) Matching placebo will be provided by Xenoport Inc.

Also known as: HORIZANT

Single Gabapentin Enacarbil Arm

Placebo DRUG

Single Gabapentin Enacarbil Arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects ages 18 to 65 years with a diagnosis of primary moderate to severe RLS
• A minimum of 6-month history of RLS symptoms
• IRLS score \>15 points (at visits 1 and 2) and a score of \> 2 on item 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)
• RLS symptoms for \>4 out of 7 evenings /day during the week prior to screening
• History of sleep disturbance due to RLS over the last 3 months
• 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
• 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
• Objective WASO of ≥30 minutes, TST \< 6.5 hours and PLMI ≥ 10 during adaptation in baseline PSG 1
• Females of child bearing potential willing to use birth control
• Subject can read understand and sign consent form
• Subject able to complete the study and to comply with study instructions and procedures

You may not qualify if:

• Subject has an apnea-hypopnea index of ≥10/ hour during adaptation/baseline night PSGs. Subjects with OSA controlled by CPAP will be accepted
• Evidence of secondary RLS
• 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)
• Clinically significant ECG abnormalities
• Any unstable medical condition that could impact subject's safety and study outcomes
• Uncontrolled hypertension at Screening or at time of treatment initiation
• Subjects diagnosed with additional sleep disorders other than RLS-associated sleep disturbance
• Neurologic disease or movement disorder, rheumatoid arthritis, fibromyalgia, uncontrolled psychiatric illness, current diagnosis or history of epilepsy or seizure disorder
• Chronic hepatitis B or hepatitis C
• Subject currently suffering from moderate or severe depression
• Subject unable to discontinue prohibited medications during the Screening period and throughout the duration of the study.
• 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.
• 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
• 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

Sponsors & Collaborators

• Cleveland Sleep Research Center: lead
• XenoPort, Inc.: collaborator
• YRT Limited: collaborator

Study Sites (1)

Cleveland Sleep Research Center

Middleburg Heights, Ohio, 44130, United States

Location

Related Publications (5)

• Winkelman JW, Shahar E, Sharief I, Gottlieb DJ. Association of restless legs syndrome and cardiovascular disease in the Sleep Heart Health Study. Neurology. 2008 Jan 1;70(1):35-42. doi: 10.1212/01.wnl.0000287072.93277.c9.

  PMID: 18166705 RESULT

• Alessandria M, Provini F. Periodic Limb Movements during Sleep: A New Sleep-Related Cardiovascular Risk Factor? Front Neurol. 2013 Aug 12;4:116. doi: 10.3389/fneur.2013.00116. eCollection 2013.

  PMID: 23964267 RESULT

• Walters AS, Rye DB. Review of the relationship of restless legs syndrome and periodic limb movements in sleep to hypertension, heart disease, and stroke. Sleep. 2009 May;32(5):589-97. doi: 10.1093/sleep/32.5.589.

  PMID: 19480225 RESULT

• Sforza E, Jouny C, Ibanez V. Time course of arousal response during periodic leg movements in patients with periodic leg movements and restless legs syndrome. Clin Neurophysiol. 2003 Jun;114(6):1116-24. doi: 10.1016/s1388-2457(03)00077-4.

  PMID: 12804680 RESULT

• Earley CJ, Silber MH. Restless legs syndrome: understanding its consequences and the need for better treatment. Sleep Med. 2010 Oct;11(9):807-15. doi: 10.1016/j.sleep.2010.07.007.

  PMID: 20817595 RESULT

MeSH Terms

Conditions

Restless Legs Syndrome

Interventions

1-(((alpha-isobutanoyloxyethoxy)carbonyl)aminomethyl)-1-cyclohexaneacetic acid; Gabapentin

Condition Hierarchy (Ancestors)

Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Parasomnias; Mental Disorders

Intervention Hierarchy (Ancestors)

Amines; Organic Chemicals; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Mansoor Ahmed, MD

  Cleveland Sleep Research Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rozina Aamir, MS, MBA

CONTACT

440-243-8044; sleepresearchcenter@yahoo.com

Zahra A Jishi, MPH

CONTACT

440-243-8044; zjishi@aol.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director

Study Record Dates

• First Submitted: April 15, 2015
• First Posted: April 23, 2015
• Study Start: June 1, 2015
• Primary Completion: June 1, 2016
• Study Completion: July 1, 2016
• Last Updated: April 23, 2015

Record last verified: 2015-04

Locations

US (1)