U.S. FDA Resources

Estimated Enrollment:	6
Study Start Date:	August 2009
Estimated Study Completion Date:	December 2011
Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Inclusion Criteria:

Subjects must meet all of the following inclusion criteria.

• AHC classic criteria:

  • Onset of symptomatology prior to 18 months of age
  • Repeated attacks of hemiplegia involving either side of the body
  • Paroxysmal disturbances, including tonic or dystonic spells, oculomotor abnormalities, and various autonomic phenomena, during hemiplegic bouts or in isolation
  • Episodes of bilateral hemiplegia or quadriplegia starting either as generalization of a hemiplegic episode or bilateral from the beginning
  • Immediate disappearance of symptoms upon sleeping, with possible resumption 10-20 minutes after waking
  • Evidence of developmental delay and neurologic abnormalities including choreoathetosis, dystonia, or ataxia

In addition:

• Provision of a complete daily event log for 6 weeks prior to initiation of sodium oxybate therapy, including the: (1) frequency, (2) duration, (3) type, (4) severity of episodes, and (5) therapies, if any, used in an attempt to abort the episode
• Ages 6 months to 25 years at the time of study enrollment
• Minimum of 3 AHC episodes weekly, lasting at least 10 minutes each, on average prior to study enrollment
• Brain neuroimaging studies excluding alternative etiology for symptoms
• Documented absence of epileptiform features on EEG during typical ictal events
• Ability of primary caregivers of study participants to submit online daily AHC Episode Logs indicating frequency and duration of ictal episodes over the entire study period
• Written informed consent from parents/guardians and assent from children 7 years or older
• Girls/women > 12 years of age will be required to be on birth control continuously if they are considered at risk to become pregnant. Those not on birth control will be required to have a screening pregnancy test at baseline, and to confirm their willingness to practice birth control or abstain from sexual activity for the duration of treatment with study medication.

Exclusion Criteria:

Subjects who meet any of the following criteria will be excluded from participation.

• History of hepatic insufficiency, renal insufficiency, significant respiratory disease, cardiac arrhythmia, congenital heart defect, hypertension, or ischemic stroke
• History of allergy/sensitivity to sodium oxybate
• Use of sodium oxybate within 30 days of study enrollment
• Serious illness requiring systemic treatment and/or hospitalization within two weeks prior to study enrollment
• Change in neurologic medication regimen within 30 days of study enrollment.
• Inability to stay at the Center for Clinical and Translational Science (CCTS) for 5 days due to behavioral issues
• Unwillingness or inability to travel to study site during the necessary 1 week titration period to determine the most appropriate dose of GHB for subsequent administration
• Noncompliance with AHC Episode Log or study visit requirements
• Sleep apnea not adequately treated with C-PAP and oxygen saturation monitoring prior to drug therapy initiation
• Succinic semialdehyde dehydrogenase deficiency

University of Utah

Alternating Hemiplegia of Childhood Foundation

Jazz Pharmaceuticals

phase I/II study effects of sodium oxybate cohort of 6 children and young adults AHC

Hemiplegia Paralysis Neurologic Manifestations Nervous System Diseases Signs and Symptoms Sodium Oxybate Adjuvants, Anesthesia Central Nervous System Agents

Therapeutic Uses Pharmacologic Actions Anesthetics, Intravenous Anesthetics, General Anesthetics Central Nervous System Depressants Physiological Effects of Drugs