An Efficacy and Safety Evaluation of HORIZANT in Adolescents With Moderate-to-Severe Primary RLS (RLS)

A Multicenter, Double-Blind, Placebo Controlled, Parallel Group, Efficacy and Safety Evaluation of HORIZANT (Gabapentin Enacarbil Extended-Release Tablets) in Adolescents Aged 13 to 17 Years Old With Moderate-to-Severe Primary RLS

The primary objective of the trial is to evaluate the efficacy of HORIZANT 300 mg and 600 mg, compared to placebo, at 12 weeks of treatment, for the treatment of Restless Legs Syndrome (RLS) in adolescents (13 to 17 years of age) diagnosed with moderate-to-severe primary RLS.

Study Overview

• Status: Recruiting
• Conditions: RLS
• Intervention / Treatment: Drug: Placebo; Drug: HORIZANT 300 mg; Drug: HORIZANT 600 mg

Detailed Description

This is a multicenter, double-blind, placebo-controlled, 3 arm, parallel group study of HORIZANT in adolescents (13 to 17 years of age) diagnosed with moderate-to-severe primary RLS. Eligible patients enter a 7-day screening period during which safety assessments are performed. Eligible patients are randomized in a 1:1:1 ratio to HORIZANT 300 mg or 600 mg, or matching placebo, followed by a 12-week treatment period. Patients take the study drug once daily at approximately 5 PM with food. Patients will visit the clinical site on 5 or 6 different occasions.

• Study Type: Interventional
• Enrollment (Anticipated): 132
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Camilla Alexander; Phone Number: 520-252-1908; Email: Camilla.Alexander@wwctrials.com

Study Locations

• United States
  • California
    • Redwood City, California, United States, 94063
      • Withdrawn
      • Stanford Sleep Medicine Center
  • Florida
    • Gulf Breeze, Florida, United States, 32561
      • Terminated
      • NW FL Clinical Research Group
    • Winter Park, Florida, United States, 32789
      • Recruiting
      • Orlando Pediatric Pulmonary and Sleep
      • Contact: Heidi Patenaude; Phone Number: 240 407-898-2767; Email: heidi@ajayihealthcare.com
      • Contact: Sarah Simonian; Phone Number: 140 4078982767; Email: paul@ajayihealthcare.com
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Withdrawn
      • PANDA Neurology/CIRCA
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Withdrawn
      • Josephson Wallack Munshower Neurology, PC
  • Missouri
    • Saint Louis, Missouri, United States, 63179
      • Recruiting
      • Pacific Research Network
      • Contact: Dixie Creager; Phone Number: 619-294-4302; Email: dcreager@prnsd.com
      • Contact: Jamie Jjirik; Email: jjirik@prnsd.com
      • Principal Investigator: Stephen Thein, MD
  • New York
    • Amherst, New York, United States, 14226
      • Withdrawn
      • Dent Neurologic Institute
  • Ohio
    • Toledo, Ohio, United States, 43608
      • Terminated
      • Mercy Health - Children's Hospital Pulmonary & Sleep Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Withdrawn
      • The Sleep Center at the Childrens Hospital of Philadelphia
  • South Carolina
    • Columbia, South Carolina, United States, 29201
      • Recruiting
      • SleepMed of South Carolina; SleepMed, Inc.
      • Contact: Natalie Scallon, CRC; Phone Number: 803-251-1093; Email: nscallon@sleepmedinc.com
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Withdrawn
      • Vanderbilt University School of Medicine
  • Texas
    • San Antonio, Texas, United States, 78249
      • Recruiting
      • Road Runner Research
      • Contact: Sandy Benavidez; Phone Number: 210-598-4314; Email: sbenavidez@rrresearchsa.com
      • Contact: Jerry Tomasovic, MD
      • Principal Investigator: Jerry Tomasovic, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 13 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and female adolescent patients, aged 13 to 17 years, diagnosed with RLS based on the IRLSSG consensus criteria (Allen RP 2014) (Appendix 2).
2. Total RLS severity score of 15 or greater on the IRLS rating scale at Visit 1 (screening) and at Visit 2 (baseline) (Appendix 8).
3. RLS symptoms for at least 4 of 7 consecutive evenings/nights during the screening period.
4. Body weight greater than 33.4 kg and a healthy weight using age-based body mass index (BMI) range 5th-95th percentile at screening and baseline.

5. Negative pregnancy test for all females at screening and baseline. Sexually active patients must agree to use 2 medically accepted methods of contraception, 1 of which is a highly effective method (e.g., hormonal or intrauterine device [IUD]) [the second may be a barrier method (e.g., male condom, female condom, diaphragm or cervical cap)], during the course of the study treatment and for 4 weeks after the last dose of study treatment. For patients using hormonal contraceptives as one of the methods, the contraceptive should be stabilized for at least 3 months prior to screening.

   Female patients who normally abstain from sexual activity may be recruited, providing they remain abstinent during the study, or if they become sexually active, they must agree to use 2 effective methods of birth control as described above.

6. Male patients must agree to use a barrier method (male condom, female condom, diaphragm, or cervical cap) with spermicide for at least 30 days prior to dosing and throughout the study, if sexually active. Male patients who normally abstain from sexual activity may be recruited, providing they remain abstinent during the study, or if they become sexually active, they must agree to use a barrier method as described above.
7. Estimated creatinine clearance of at least 60 mL/min (using the Cockcroft-Gault equation) at screening only.
8. Appropriate cognitive and communication skills, as judged by the clinician, needed to complete study assessments.
9. Signed patient and parent Institutional Review Board (IRB)-approved informed consent/assent form (as applicable) before any study-related procedures are performed.
10. Willing and able to follow the study procedures.

Exclusion Criteria:

1. History of a primary sleep disorder other than RLS that may significantly affect the symptoms of RLS.
2. Serum ferritin level < 20 ng/mL at screening.
3. History of allergy, hypersensitivity, or intolerance to HORIZANT or any other gabapentin products (e.g., Neurontin®, Gralise®).
4. Suffering from an isolated periodic limb movement disorder without RLS.
5. Currently meet Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DSM-5) criteria for substance use disorder, or history thereof, within 12 months before dosing.
6. Current or past history of any significant psychiatric disorder including, but not limited to, depression (treatment with antidepressants), bipolar disorder, or schizophrenia.
7. Diagnosis of ADHD is allowed, provided the patient is not receiving medication(s) known to affect the assessment of RLS.
8. History of suicidal behavior or suicidal ideation as indicated by the C-SSRS, administered at screening, and as per investigator's judgment.
9. Patients with a history of epilepsy, subjects currently prescribed treatments for epilepsy, or subjects with a history of seizure in the last 5 years.
10. Medical condition or disorder that would interfere with the action, absorption, distribution, metabolism, or excretion of gabapentin enacarbil, or, in the Principal Investigator's judgment is considered to be clinically significant and may pose a safety concern, or, could interfere with the accurate assessment of safety or efficacy, or could potentially affect a patient's safety or study outcome.
11. In the judgement of the Principal Investigator, clinically significant, abnormal laboratory result or physical examination finding not resolved by the time of baseline assessments.
12. Positive test for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody at screening.
13. Uncontrolled hypertension defined as blood pressure (BP) ≥ 95 percentile adjusted for age, height, and sex, according to the tables published by the US Department of Health and Human Services 2005, at screening and before dosing. Appendix 5 contains the tables that can be consulted.
14. Participated in an investigational drug trial within the 4 weeks before dosing or plans to participate in another study at any time during this study.
15. Received an investigational product within 6 months prior to dosing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo once daily	Drug: Placebo; Placebo once daily
Experimental: HORIZANT 300 mg; HORIZANT 300 mg once daily	Drug: HORIZANT 300 mg; HORIZANT 300 mg once daily; Other Names: Gabapentin Enacarbil Extended-Release Tablets
Experimental: HORIZANT 600 mg; HORIZANT 600 mg once daily	Drug: HORIZANT 600 mg; HORIZANT 600 mg once daily; Other Names: Gabapentin Enacarbil Extended-Release Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the change on the IRLS rating scale from baseline to Week 12	IRLS rating change	12 weeks
the proportion of patients who are responders, assessed on the CGI-I scale as "much improved" or "very much improved" (CGI-I rating of 1 or 2, respectively) at Week 12	CGI-I scale	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IRLS total score, change from baseline to Weeks 4 and 8	IRLS change	4, 8 weeks
CGI-I score at Weeks 4 and 8	CGI-I score	4, 8 weeks
Proportions of patients by sleep parameters collected on the Post-Sleep questionnaire at baseline and Week 12	sleep parameters on Post-Sleep questionnaire	Baseline to 12 weeks
Proportions of patients by sleep parameters collected on the ESS-CHAD© total score and change from baseline to Week 12	sleep parameters by ESS-CHAD© total score and change	Baseline to 12 weeks
Proportions of patients with AEs, fatal serious adverse events (SAEs), non-fatal SAEs, and discontinuations due to AEs at all post-dose time points; and proportion of patients with neuropsychiatric AEs	Adverse event proporations	12 weeks

Collaborators and Investigators

• Sponsor: XenoPort, Inc.
• Investigators: Study Director: Steven Caras, MD, Xenoport/Arbor Pharmaceuticals, LLC

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2016
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): October 1, 2023

Study Registration Dates

• First Submitted: September 23, 2015
• First Submitted That Met QC Criteria: September 24, 2015
• First Posted (Estimate): September 25, 2015

Study Record Updates

• Last Update Posted (Actual): June 9, 2021
• Last Update Submitted That Met QC Criteria: June 7, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: RLS; Restless Leg Syndrome
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Anti-Anxiety Agents; Anticonvulsants; Antimanic Agents; Gabapentin
• Other Study ID Numbers: XP109