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

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.

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.