A PK and Safety Evaluation of HORIZANT (Gabapentin Enacarbil) in Adolescents With Moderate-to-Severe Primary RLS (RLS)

A Multicenter, Open-label, Single-dose Pharmacokinetic and Safety Evaluation of HORIZANT (Gabapentin Enacarbil Extended-release Tablets) in Adolescents Aged 13 to 17 Years Old With Moderate-to-severe Primary Restless Legs Syndrome

The primary objective is to assess the pharmacokinetics (PK) of gabapentin following the single-dose administration of HORIZANT (Gabapentin Enacarbil) in adolescents (13 to 17 years of age) diagnosed with moderate-to-severe Primary Restless Legs Syndrome (RLS).

Study Overview

• Status: Withdrawn
• Conditions: RLS
• Intervention / Treatment: Drug: HORIZANT 300 mg

Detailed Description

One-treatment, 1-period study in adolescents (13 to 17 years of age) diagnosed with moderate-to-severe primary RLS. Patients will check-in at the clinical site in the evening of Day -1 or the morning of Day 0, and baseline safety assessments will be performed. On Day 0, after the review of these safety assessments and confirmation of eligibility, patients will receive a single oral 300 mg dose of HORIZANT with a meal (at approximately 6 AM). Study assessments will continue until approximately 14 hours (h) post dose, at which time patients will be discharged. Prior to discharge, patients will be advised not to drive a car or operate other complex machinery for at least 30 h after dosing; therefore, patients can remain at the clinical site overnight or can be escorted home. Patients will return to the clinical site for a follow-up visit 7 days (± 1 day) post dose.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Redwood City, California, United States, 94063
      • Stanford Sleep Medicine Center
  • Missouri
    • Saint Louis, Missouri, United States, 63179
      • Pacific Research Network
  • South Carolina
    • Columbia, South Carolina, United States, 29201
      • SleepMed of South Carolina; SleepMed, Inc.
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 17 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, which is presented in Appendix 2.
2. Total RLS severity score of 15 or greater on the IRLS rating scale at screening.
3. Body weight greater than 33.4 kg and a healthy weight using age-based body mass index (BMI) range 5th to 85th percentile. Appendix 3 contains BMI-for-age charts that can be consulted.

4. Negative pregnancy test for females of childbearing potential. Female patients of childbearing potential must agree to use one of the following acceptable birth control methods:

   1. intrauterine device in place for at least 3 months prior to dosing
   2. barrier methods (male condom, female condom, diaphragm or cervical cap) with spermicide for at least 30 days prior to dosing and throughout the study
   3. stable hormonal contraceptive (including oral, injection, or implants) for at least 3 months prior to dosing and throughout the study 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 effective methods of birth control as described above.
5. Male patients able to father a child 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. 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.
6. Signed patient/parent Institutional Review Board (IRB)-approved informed consent/assent form (as applicable) prior to any study procedures.

Exclusion Criteria:

1. History of allergy, hypersensitivity or intolerance to HORIZANT or any other gabapentin compounds.
2. Suffering from a movement disorder that could mimic or confound the accurate diagnosis of RLS (eg, Tourette's syndrome, tic disorder, periodic limb movement disorder [PLMD], sleep disorders).
3. Currently meet Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DSM-5) criteria for substance use disorder, or history thereof, within 12 months prior to dosing.
4. Current or past history of any significant psychiatric disorder including but not limited to depression (treatment with antidepressants), bipolar disorder or schizophrenia.
5. History of suicidal behavior or suicidal ideation as indicated by the Columbia Suicide Severity Rating Scale (C-SSRS), administered at screening (the questionnaire is presented in Appendix 4), and as per investigator's judgment.
6. History of seizure disorder or at increased risk for development of a seizure disorder, including but not limited to complicated febrile seizure and history of significant head injury.
7. Medical condition or disorder that would interfere with the action, absorption, distribution, metabolism, or excretion of gabapentin enacarbil, or, in the 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HORIZANT 300 mg; HORIZANT 300 mg once daily	Drug: HORIZANT 300 mg; HORIZANT 300 mg once daily; Other Names: gabapentin enacarbil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the concentration-time curve from the time of dosing to the last measurable concentration (AUC0-tlast).	AUCtlast	0-14 hours
Area under the concentration-time curve from the time of dosing extrapolated to infinity (AUCinf)	AUCinf	0-14 hours
Percentage of AUCinf that is extrapolated from time of last measurable concentration to infinity (AUCextr%)	% AUCinf	0-14 hours
Maximum observed plasma drug concentration (Cmax)	Cmax	0-14 hours
Time to maximum concentration (Tmax)	Tmax	0-14 hours
Apparent elimination half-life (T1/2)	T1/2	0-14 hours
Apparent oral clearance (CL/F)	CL/F	0-14 hours
Apparent oral volume of distribution (Vd/F)	Vd/F	0-14 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)	Columbia-Suicide Severity Rating Scale (C-SSRS)	7 days

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): January 1, 2016
• Primary Completion (Actual): July 19, 2017
• Study Completion (Actual): July 19, 2017

Study Registration Dates

• First Submitted: December 10, 2015
• First Submitted That Met QC Criteria: December 14, 2015
• First Posted (Estimate): December 17, 2015

Study Record Updates

• Last Update Posted (Actual): April 12, 2021
• Last Update Submitted That Met QC Criteria: April 7, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Restless Legs Syndrome; RLS
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Parasomnias; Restless Legs Syndrome; 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: XP108

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO