Exploratory Clinical Study to Evaluate Sodium Oxybate (Xyrem) on Potential Endocrine Changes

Primary Outcomes

• The Insulin-like Growth Factor 1 (IGF-1) Measured in Fasting Conditions at Baseline (Visit 2) Baseline (Visit 2) - approximately 1 day

  An assay of IGF-1 was done from blood sampled about 10 hours after bedtime on Visit 2.

• The Insulin-like Growth Factor 1 (IGF-1) Measured in Fasting Conditions After 1 Month of Treatment (Visit 3) After 1 month of treatment (Visit 3)

  An assay of IGF-1 was done from blood sampled about 10 hours postdose on Visit 3.

• The Insulin-like Growth Factor 1 (IGF-1) Measured in Fasting Conditions After 3 Months of Treatment (Visit 4) After 3 months of treatment (Visit 4)

  An assay of IGF-1 was done from blood sampled about 10 hours postdose on Visit 4.

Secondary Outcomes

• The Circadian Rhythm of the Growth Hormone (GH) Measured at Baseline (Visit 2) Baseline (Visit 2) - approximately 1 day

  Blood was sampled at Baseline (Visit 2) at bedtime 10:00 pm and 1, 2, 4, 8, 12, 16, and 20 hours after bedtime for assaying GH.

• The Circadian Rhythm of the Growth Hormone (GH) Measured at Visit 3 Visit 3 (approximately 1 month)

  Blood was sampled predose and 1, 2, 4, 8, 12, 16, and 20 hours postdose at Visit 3 for assaying GH.

• The Circadian Rhythm of the Growth Hormone (GH) Measured at Visit 4 Visit 4 (approximately 3 months)

  Blood was sampled predose and 1, 2, 4, 8, 12, 16, and 20 hours postdose at Visit 4 for assaying GH.

• Cortisol Measured at Baseline (Visit 2) Baseline (Visit 2) - approximately 1 day

  Blood was sampled at Baseline (Visit 2) at bedtime 10:00 pm and 1, 2, 4, 8, 12, 16, and 20 hours after bedtime for assaying cortisol.

• Cortisol Measured at Visit 3 Visit 3 (approximately 1 month)

  Blood was sampled predose and and 1, 2, 4, 8, 12, 16, and 20 hours postdose at Visit 3 for assaying cortisol.

• Cortisol Measured at Visit 4 Visit 4 (approximately 3 months)

  Blood was sampled predose and 1, 2, 4, 8, 12, 16, and 20 hours postdose at Visit 4 for assaying cortisol.

• The Adrenocorticotropic Hormone (ACTH) Measured in Fasting Conditions at Baseline (Visit 2) Baseline (Visit 2) - approximately 1 day

  An assay of ACTH was done from blood sampled about 10 hours after bedtime on Visit 2.

• The Adrenocorticotropic Hormone (ACTH) Measured in Fasting Conditions at Visit 3 Visit 3 (approximately 1 month)

  An assay of ACTH was done from blood sampled about 10 hours postdose on Visit 3.

• The Adrenocorticotropic Hormone (ACTH) Measured in Fasting Conditions at Visit 4 Visit 4 (approximately 3 months)

  An assay of ACTH was done from blood sampled about 10 hours postdose on Visit 4.

• The Dehydroepiandrosterone Sulfate (DHEA-S) Measured in Fasting Conditions at Baseline (Visit 2) Baseline (Visit 2) - approximately 1 day

  An assay of DHEA-S was done from blood sampled about 10 hours after bedtime on Visit 2.

• The Dehydroepiandrosterone Sulfate (DHEA-S) Measured in Fasting Conditions at Visit 3 Visit 3 (approximately 1 month)

  An assay of DHEA-S was done from blood sampled about 10 hours postdose on Visit 3.

• The Dehydroepiandrosterone Sulfate (DHEA-S) Measured in Fasting Conditions at Visit 4 Visit 4 (approximately 3 months)

  An assay of DHEA-S was done from blood sampled about 10 hours postdose on Visit 4.

• The Prolactin Measured in Fasting Conditions at Baseline (Visit 2) Baseline (Visit 2) - approximately 1 day

  An assay of prolactin was done from blood sampled about 10 hours after bedtime on Visit 2.

• The Prolactin Measured in Fasting Conditions at Visit 3 Visit 3 (approximately 1 month)

  An assay of prolactin was done from blood sampled about 10 hours postdose on Visit 3.

• The Prolactin Measured in Fasting Conditions at Visit 4 Visit 4 (approximately 3 months)

  An assay of prolactin was done from blood sampled about 10 hours postdose on Visit 4.

• The Thyroid Stimulating Hormone (TSH) Measured in Fasting Conditions at Baseline (Visit 2) Baseline (Visit 2) - approximately 1 day

  An assay of TSH was done from blood sampled about 10 hours after bedtime on Visit 2.

• The Thyroid Stimulating Hormone (TSH) Measured in Fasting Conditions at Visit 3 Visit 3 (approximately 1 month)

  An assay of TSH was done from blood sampled about 10 hours postdose on Visit 3.

• The Thyroid Stimulating Hormone (TSH) Measured in Fasting Conditions at Visit 4 Visit 4 (approximately 3 months)

  An assay of TSH was done from blood sampled about 10 hours postdose on Visit 4.

• The Total Thyroxin (T4) Measured in Fasting Conditions at Baseline (Visit 2) Baseline (Visit 2) - approximately 1 day

  An assay of T4 was done from blood sampled about 10 hours after bedtime on Visit 2.

• The Total Thyroxin (T4) Measured in Fasting Conditions at Visit 3 Visit 3 (approximately 1 month)

  An assay of T4 was done from blood sampled about 10 hours postdose on Visit 3.

• The Total Thyroxin (T4) Measured in Fasting Conditions at Visit 4 Visit 4 (approximately 3 months)

  An assay of T4 was done from blood sampled about 10 hours postdose on Visit 4.

• The Osmolality Measured in Fasting Conditions at Baseline (Visit 2) Baseline (Visit 2) - approximately 1 day

  An assay of osmolality was done from blood sampled about 10 hours after bedtime on Visit 2.

• The Osmolality Measured in Fasting Conditions at Visit 3 Visit 3 (approximately 1 month)

  An assay of osmolality was done from blood sampled about 10 hours postdose on Visit 3.

• The Osmolality Measured in Fasting Conditions at Visit 4 Visit 4 (approximately 3 months)

  An assay of osmolality was done from blood sampled about 10 hours postdose on Visit 4.

• Electrolytes (Na, K, Ca) Measured in Fasting Conditions at Baseline (Visit 2) Baseline (Visit 2) - approximately 1 day

  An assay of electrolytes was done from blood sampled about 10 hours after bedtime on Visit 2.

• The Electrolyte Phosphate (P) Measured in Fasting Conditions at Baseline (Visit 2) Baseline (Visit 2) - approximately 1 day

  An assay of electrolytes was done from blood sampled about 10 hours after bedtime on Visit 2.

• Electrolytes (Na, K, Ca) Measured in Fasting Conditions at Visit 3 Visit 3 (approximately 1 month)

  An assay of electrolytes was done from blood sampled about 10 hours postdose on Visit 3.

• The Electrolyte Phosphate (P) Measured in Fasting Conditions at Visit 3 Visit 3 (approximately 1 month)

  An assay of electrolytes was done from blood sampled about 10 hours postdose on Visit 3.

• Electrolytes (Na, K, Ca) Measured in Fasting Conditions at Visit 4 Visit 4 (approximately 3 months)

  An assay of electrolytes was done from blood sampled about 10 hours postdose on Visit 4.

• The Electrolyte Phosphate (P) Measured in Fasting Conditions at Visit 4 Visit 4 (approximately 3 months)

  An assay of electrolytes was done from blood sampled about 10 hours postdose on Visit 4.

• The Number of Patients Reporting at Least One Adverse Event (AE) During the Course of the Study Visit 1 through the end of the study (approximately 4 months)

  An AE was classified as a treatment-emergent AE (TEAE) if its onset date and time was on or after the first study drug administration. Number of subjects with at least one TEAE is reported below.

• The Number of Patient Withdrawal Due to Adverse Events (AEs) During the Course of the Study Visit 1 through the end of the study (approximately 4 months)

  An AE was classified as a treatment-emergent AE (TEAE) if its onset date and time was on or after the first study drug administration. Number of subjects with TEAE that led to temporarily discontinuation of study drug is reported below.

• The Number of Patients Reporting at Least One Serious Adverse Event (SAE) During the Course of the Study Visit 1 through the end of the study (approximately 4 months)

  A Serious Adverse Event is any untoward medical occurrence that at any dose • results in death, • is life threatening, • requires in-patient hospitalization or prolongation of existing hospitalization, • results in persistent or significant disability/incapacity • is a congenital anomaly/birth defect