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

• ClinicalTrials.gov Identifier: NCT02560766
• Recruitment Status: Recruiting
• First Posted: September 25, 2015
• Last Update Posted: June 9, 2021
• Sponsor: XenoPort, Inc.
• Information provided by (Responsible Party): XenoPort, Inc.

Study Description

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 Design

• 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

Arms and Interventions

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

Outcome Measures

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Camilla Alexander; 520-252-1908; Camilla.Alexander@wwctrials.com

Locations

United States, California

Stanford Sleep Medicine Center; Withdrawn

Redwood City, California, United States, 94063

United States, Florida

NW FL Clinical Research Group; Terminated

Gulf Breeze, Florida, United States, 32561

Orlando Pediatric Pulmonary and Sleep; Recruiting

Winter Park, Florida, United States, 32789

Contact: Heidi Patenaude 407-898-2767 ext 240 heidi@ajayihealthcare.com

Contact: Sarah Simonian 4078982767 ext 140 paul@ajayihealthcare.com

Principal Investigator: Akinyemi Ajayi, MD

United States, Georgia

PANDA Neurology/CIRCA; Withdrawn

Atlanta, Georgia, United States, 30328

United States, Indiana

Josephson Wallack Munshower Neurology, PC; Withdrawn

Indianapolis, Indiana, United States, 46256

United States, Missouri

Pacific Research Network; Recruiting

Saint Louis, Missouri, United States, 63179

Contact: Dixie Creager 619-294-4302 dcreager@prnsd.com

Contact: Jamie Jjirik jjirik@prnsd.com

Principal Investigator: Stephen Thein, MD

United States, New York

Dent Neurologic Institute; Withdrawn

Amherst, New York, United States, 14226

United States, Ohio

Mercy Health - Children's Hospital Pulmonary & Sleep Center; Terminated

Toledo, Ohio, United States, 43608

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 nscallon@sleepmedinc.com

Principal Investigator: Richard Bogan, MD

United States, Tennessee

Vanderbilt University School of Medicine; Withdrawn

Nashville, Tennessee, United States, 37232

United States, Texas

Road Runner Research; Recruiting

San Antonio, Texas, United States, 78249

Contact: Sandy Benavidez 210-598-4314 sbenavidez@rrresearchsa.com

Contact: Jerry Tomasovic, MD

Principal Investigator: Jerry Tomasovic, MD

Sponsors and Collaborators

XenoPort, Inc.

Investigators

• Study Director: Steven Caras, MD; Xenoport/Arbor Pharmaceuticals, LLC

More Information

• Responsible Party: XenoPort, Inc.
• ClinicalTrials.gov Identifier: NCT02560766
• Other Study ID Numbers: XP109
• First Posted: September 25, 2015
• Last Update Posted: June 9, 2021
• Last Verified: June 2021

Keywords provided by XenoPort, Inc.:

Restless Leg Syndrome; RLS

Additional relevant MeSH terms:

Gabapentin; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anticonvulsants; Anti-Anxiety Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antimanic Agents