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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02560766
Recruitment Status : Recruiting
First Posted : September 25, 2015
Last Update Posted : December 3, 2018
Information provided by (Responsible Party):
XenoPort, Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
RLS Drug: HORIZANT 300 mg Drug: HORIZANT 600 mg Drug: Placebo Phase 4

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  (Clinical Trial)
Estimated Enrollment : 132 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : February 2016
Estimated Primary Completion Date : October 2023
Estimated Study Completion Date : October 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Restless Legs

Arm Intervention/treatment
Experimental: HORIZANT 300 mg
HORIZANT 300 mg once daily
Drug: HORIZANT 300 mg
HORIZANT 300 mg once daily
Other Name: Gabapentin Enacarbil Extended-Release Tablets

Experimental: HORIZANT 600 mg
HORIZANT 600 mg once daily
Drug: HORIZANT 600 mg
HORIZANT 600 mg once daily
Other Name: Gabapentin Enacarbil Extended-Release Tablets

Placebo Comparator: Placebo
Placebo once daily
Drug: Placebo
Placebo once daily

Primary Outcome Measures :
  1. the change on the IRLS rating scale from baseline to Week 12 [ Time Frame: 12 weeks ]
    IRLS rating change

  2. 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 [ Time Frame: 12 weeks ]
    CGI-I scale

Secondary Outcome Measures :
  1. IRLS total score, change from baseline to Weeks 4 and 8 [ Time Frame: 4, 8 weeks ]
    IRLS change

  2. CGI-I score at Weeks 4 and 8 [ Time Frame: 4, 8 weeks ]
    CGI-I score

  3. Proportions of patients by sleep parameters collected on the Post-Sleep questionnaire at baseline and Week 12 [ Time Frame: Baseline to 12 weeks ]
    sleep parameters on Post-Sleep questionnaire

  4. Proportions of patients by sleep parameters collected on the ESS-CHAD© total score and change from baseline to Week 12 [ Time Frame: Baseline to 12 weeks ]
    sleep parameters by ESS-CHAD© total score and change

  5. 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 [ Time Frame: 12 weeks ]
    Adverse event proporations

Information from the National Library of Medicine

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Ages Eligible for Study:   13 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02560766

Contact: Camilla Alexander 520-252-1908

United States, California
Stanford Sleep Medicine Center Recruiting
Redwood City, California, United States, 94063
Contact: Michelle Kim, RN    650-721-7576   
Principal Investigator: Clete Kushida, MD         
Pacific Research Network, LLC Recruiting
San Diego, California, United States, 92103
Contact: Stephen Thein, MD    619-936-8102   
Principal Investigator: Stephen Thein, MD         
United States, Florida
NW FL Clinical Research Group Not yet recruiting
Gulf Breeze, Florida, United States, 32561
Contact: Genei Bougher    805-934-1299   
Contact: S Colbert   
Principal Investigator: Gulner Com, MD         
Orlando Pediatric Pulmonary and Sleep Recruiting
Winter Park, Florida, United States, 32789
Contact: Heidi Patenaude, MD    407-898-2767   
Contact: Paul   
Principal Investigator: Akinyemi Ajayi, MD         
United States, Georgia
PANDA Neurology/CIRCA Recruiting
Atlanta, Georgia, United States, 30328
Contact: Catherine Noie    678-705-7341   
Contact: J Robert Flamini, MD    678-973-0578   
Principal Investigator: J Robert Flamini, MD         
United States, Indiana
Josephson Wallack Munshower Neurology, PC Recruiting
Indianapolis, Indiana, United States, 46256
Contact: Kristi Mann    317-537-6088 ext 1229   
Contact: Kristina Cleveland    317-806-6965   
United States, Missouri
Pacific Research Network Recruiting
Saint Louis, Missouri, United States, 63179
Contact: Dixie Creager    619-294-4302   
Contact: Jamie Jjirik   
Principal Investigator: Stephen Thein, MD         
United States, New York
Dent Neurologic Institute Recruiting
Amherst, New York, United States, 14226
Contact: Caroline Kumm    716-558-3492   
Contact: A Jamison   
Principal Investigator: Kenneth Murray, MD         
United States, Ohio
Mercy Pediatric Pulmonary Specialists Recruiting
Toledo, Ohio, United States, 43608
Contact: Darla Scott    419-251-6430   
Contact: Reddy Ramalinga, MD   
Principal Investigator: Reddy Ramalinga, MD         
United States, Pennsylvania
The Sleep Center at the Childrens Hospital of Philadelphia Withdrawn
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
SleepMed of South Carolina; SleepMed, Inc. Recruiting
Columbia, South Carolina, United States, 29201
Contact: Natalie Scallon, CRC    803-251-1093   
Principal Investigator: Richard Bogan, MD         
United States, Tennessee
Vanderbilt University School of Medicine Recruiting
Nashville, Tennessee, United States, 37232
Contact: Wendi Welch    615-936-8102   
Contact: Mary Keener   
Principal Investigator: Arthur Walters, MD         
United States, Texas
Road Runner Research Recruiting
San Antonio, Texas, United States, 78249
Contact: Sandy Benavidez    210-598-4314   
Contact: Jerry Tomasovic, MD         
Principal Investigator: Jerry Tomasovic, MD         
Sponsors and Collaborators
XenoPort, Inc.
Study Director: Steven Caras, MD Xenoport/Arbor Pharmaceuticals, LLC

Responsible Party: XenoPort, Inc. Identifier: NCT02560766     History of Changes
Other Study ID Numbers: XP109
First Posted: September 25, 2015    Key Record Dates
Last Update Posted: December 3, 2018
Last Verified: November 2018

Keywords provided by XenoPort, Inc.:
Restless Leg Syndrome

Additional relevant MeSH terms:
gamma-Aminobutyric Acid
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antiparkinson Agents
Anti-Dyskinesia Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Antimanic Agents
GABA Agents