Carolina Fragile X Project Continuous Performance Test

“Subjects were recruited from fragile X clinics at Rush University Medical Center (RUMC) and the MIND Institute at University of California at Davis Medical Center (UCDMC). Informed written consent was obtained from either the subject or the parent before participation.”

“At the screening visit medical history, exam, vital signs, laboratory testing including routine chemistries, blood counts, thyroid functions, electrocardiogram (ECG), and a pregnancy test (females) were evaluated”

“laboratory testing including routine chemistries, blood counts, thyroid functions, electrocardiogram (ECG), and a pregnancy test (females) were evaluated”

“baseline CPT (Carolina Project Fragile X continuous performance test) and prepulse inhibition (PPI) outcome measures were obtained”

“baseline CPT (Carolina Project Fragile X continuous performance test) and prepulse inhibition (PPI) outcome measures were obtained”

“At the treatment visit, 14–28 days after screening, an IV was inserted for blood drawing and the subject received the study medication orally.”

“At the treatment visit, 14–28 days after screening, an IV was inserted for blood drawing and the subject received the study medication orally.”

“The first subject for each gender was dosed with 50 mg fenobam, the second with 100 mg, and all subsequent subjects with 150 mg.”

“Blood for pharmacokinetic testing, blood pressure, heart rate and side effect screening was obtained at 0, 15, 30, 45, 60, 120, 180, 240, 300, and 360 min after dosing.”

“Blood for pharmacokinetic testing, blood pressure, heart rate and side effect screening was obtained at 0, 15, 30, 45, 60, 120, 180, 240, 300, and 360 min after dosing.”

“Blood for pharmacokinetic testing, blood pressure, heart rate and side effect screening was obtained at 0, 15, 30, 45, 60, 120, 180, 240, 300, and 360 min after dosing.”

“Blood for pharmacokinetic testing, blood pressure, heart rate and side effect screening was obtained at 0, 15, 30, 45, 60, 120, 180, 240, 300, and 360 min after dosing.”

“Blood for pharmacokinetic testing, blood pressure, heart rate and side effect screening was obtained at 0, 15, 30, 45, 60, 120, 180, 240, 300, and 360 min after dosing.”

“Post-treatment PPI was performed after the 60 min blood sampling, followed by CPT.”

“Startle stimuli (SS) were 50 ms 105 db SPL white noise pulses and acoustic prepulses (PP) are 25 ms 75 db SPL 1 kHz tones. These trials are delivered while participants watch a silent movie to maintain compliance and interest in the procedure.”

“we eliminated the 60 ms trial type and added two trials per type, resulting in a protocol with 30 total trials (10 with SS alone, 10 with 120 ms prepulse and 10 with 240 ms prepulse)”

“we eliminated the 60 ms trial type and added two trials per type, resulting in a protocol with 30 total trials (10 with SS alone, 10 with 120 ms prepulse and 10 with 240 ms prepulse)”

“Blood for pharmacokinetic testing, blood pressure, heart rate and side effect screening was obtained at 0, 15, 30, 45, 60, 120, 180, 240, 300, and 360 min after dosing.”

“Post-treatment PPI was performed after the 60 min blood sampling, followed by CPT.”

“Blood for pharmacokinetic testing, blood pressure, heart rate and side effect screening was obtained at 0, 15, 30, 45, 60, 120, 180, 240, 300, and 360 min after dosing.”

“Blood for pharmacokinetic testing, blood pressure, heart rate and side effect screening was obtained at 0, 15, 30, 45, 60, 120, 180, 240, 300, and 360 min after dosing.”

“Blood for pharmacokinetic testing, blood pressure, heart rate and side effect screening was obtained at 0, 15, 30, 45, 60, 120, 180, 240, 300, and 360 min after dosing.”

“Blood for pharmacokinetic testing, blood pressure, heart rate and side effect screening was obtained at 0, 15, 30, 45, 60, 120, 180, 240, 300, and 360 min after dosing.”

“Our side effects screening protocol involved asking both the subject and family members if the subject was having any of a structured list of symptoms relevant to potential effects of fenobam (aggression, fatigue, hyperactivity, anxiety and fidgetiness, increase in self stimulation, odd behaviour, inappropriate laughter, dizziness, vertigo, nausea, paraesthesia, and headache)”

“and direct observation by the physician and family for the above symptoms and other behavioural changes”

“Conference calls were held after each subject was dosed, to confirm absence of adverse events and justify dose escalation or maintenance for the subsequent subject of that gender.”

“Fenobam concentrations from plasma samples were measured with MS-MS based assays validated for human application, using positive ion liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS).”

“PPI was calculated as: 100 × [(mean response magnitude in the startle stimulus alone trials – mean response magnitude in the prepulse trials)/mean response magnitude in the startle stimulus alone trials].”

“we determined a priori that subjects with PPI improvement of 20% on the 120 ms trials (the most reliable trial latency) or more would be considered responders.”

“the number of correct hits on a target stimuli, omissions involving lack of reaction to a target (attention deficit), and commissions involving reacting to a non-target (impulsivity, poor inhibitory control) were tabulated.”

“For statistical analysis of PPI data, a positive response was defined as a 20% or greater improvement over baseline. One sample exact binomial 95% confidence interval was computed for the proportion of positive response.”