Wigal 2013.

Methods	4‐6 weeks open‐label treatment (dose optimisation), cross‐over, and 2‐week double‐blind with 2 interventions: Methylphenidate (NWP06 ‐ liquid formulation of extended release methylphenidate) Placebo
Participants	Number of participants screened: 45 Number of participants included: 44 Number of participants followed up: 39 Number of withdrawals: 6 Diagnosis of ADHD: DSM‐IV diagnosis of ADHD (subtype: combined (70.5%), hyperactive‐impulsive (2.3%), inattentive (27.3%)) Age: mean 8.8, range 6‐12 years old IQ: not stated Sex: 32 males, 12 females Methylphenidate‐naïve: none Ethnicity: white (79.5%), Black/African American (9.1%); Asian (6.8%); other (4.5%) Country: USA Comorbidity: elimination disorder (9.1%); oppositional defiant disorder (18.2%); specific phobias (4.5%) Comedication: none Sociodemographics: not stated Inclusion criteria ADHD diagnosis by psychiatrist, psychologist, developmental paediatrician, or paediatrician Pharmacological treatment for ADHD and either experienced suboptimal efficacy, a safety or tolerability issue with their current regimen, or been in need of a long‐acting liquid formulation CGI‐S score ≥ 3 ≥ 90th percentile for age and gender on the ADHD‐RS (either total score, or hyperactive‐impulsive subscale or inattentive subscale) Exclusion criteria Comorbidity (DSM‐IV axis I), with the exceptions of: specific phobia, motor skills disorders, oppositional defiant disorder, sleep disorders, elimination disorders, adjustment disorders, learning disorders, or communication disorders IQ lower than 80 Chronic disease: seizure disorder, thyroid disease, Tourette disorder or family history of Tourette disorder or tics, serious cardiac conditions, cardiomyopathy, serious arrhythmias, structural cardiac disorders, glaucoma, or severe hypertension. Any investigational medication 15 days prior screening Atomoxetine or monoamine oxidase inhibitor 30 days prior screening
Interventions	Participants were randomly assigned to different sequences of methylphenidate and placebo Methylphenidate type: liquid formulation of extended release methylphenidate Mean methylphenidate dosage: 32.8 mg/day Administration schedule: 4 times daily Duration of each medication condition: 1 week Washout prior to study initiation: yes (1 day for stimulants) Medication‐free period between intervention: no Titration period: 3 weeks initiated before randomisation Treatment compliance: 2 withdrawals of assent/consent, 2 adverse events, 1 lack of efficacy, 1 lost to follow‐up
Outcomes	ADHD symptoms ‐ SKAMP, ADHD‐RS (open‐label phase) Non‐serious adverse events 42 participants (93.3%) experienced a treatment‐emergent adverse event 3 (6.7%) participants with severe (affect lability, aggression, and initial insomnia) and 2 (4.4%) participants had to discontinue medication (affect lability and aggression) Open‐label phase: decreased appetite (55.6%), abdominal pain upper (42.2%), affect lability (26.7%), initial insomnia (22.2%), insomnia (17.8%), and headache (17.8%) Other AEs reported in ≥ 5% of the participants during the open phase: vomiting, diarrhoea, logorrhea, aggression, dizziness, irritability, fatigue, upper respiratory tract infection, cough, and flushing Double‐blind phase: 11 (24.4%) participants had a AE while receiving NWP06 and 5 (11.1%) participants had a AE while receiving placebo
Notes	Sample calculation: no Ethics approval: yes Key conclusions from study authors: NWP06 resulted in significant improvements in the SKAMP‐combined score at 4 hours post‐dose as compared with placebo in the completers. This study shows that NWP06 significantly improved ADHD symptoms in school‐aged children and was well tolerated Comments from the study authors: "This study of NWP06 allowed inclusion of patients who were either treatment naïve or had previously been treated with stimulants" "Subjects were required to have been in need of pharmacological treatment for ADHD" "Our population more closely reflects a real‐world population and provides a more rigorous test of the study drug." Comments from the review authors: laboratory school environment, and lack of the ADHD‐RS. Race/ethnicity doesn't reflect a real‐world population Exclusion of methylphenidate non‐responders/children who have previously experienced adverse events on methylphenidate: not clear Supplemental information requested from study authors in August 2014. No reply