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The Efficacy and Safety of Evekeo, Racemic Amphetamine Sulfate, for Treatment of Attention-Deficit/Hyperactivity Disorder Symptoms: A Multicenter, Dose-Optimized, Double-Blind, Randomized, Placebo-Controlled Crossover Laboratory Classroom Study.

Childress AC, Brams M, Cutler AJ, Kollins SH, Northcutt J, Padilla A, Turnbow JM - J Child Adolesc Psychopharmacol (2015)

Bottom Line: Compared to placebo, a single daily dose of R-AMPH significantly improved SKAMP-Combined scores (p<0.0001) at each time point tested throughout the laboratory classroom days, with effect onset 45 minutes postdose and extending through 10 hours.R-AMPH significantly improved PERMP number of problems attempted and correct (p<0.0001) throughout the laboratory classroom days.TEAEs and changes in vital signs associated with R-AMPH were generally mild and not unexpected.

View Article: PubMed Central - PubMed

Affiliation: 1 Center for Psychiatry and Behavioral Medicine , Las Vegas, Nevada.

ABSTRACT

Objective: The study goal was to determine the efficacy and safety of an optimal dose of Evekeo, racemic amphetamine sulfate, 1:1 d-amphetamine and l-amphetamine (R-AMPH), compared to placebo in treating children with attention-deficit/hyperactivity disorder (ADHD) in a laboratory classroom setting.

Methods: A total of 107 children ages 6-12 years were enrolled in this multicenter, dose-optimized, randomized, double-blind, placebo-controlled crossover study. After 8 weeks of open-label dose optimization, 97 subjects were randomized to 2 weeks of double-blind treatment in the sequence of R-AMPH followed by placebo (n=47) or placebo followed by R-AMPH (n=50). Efficacy measures included the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale and Permanent Product Measure of Performance (PERMP) administered predose and at 0.75, 2, 4, 6, 8, and 10 hours postdose on 2 laboratory classroom days. Safety assessments included physical examination, chemistry, hematology, vital signs, and treatment-emergent adverse events (TEAEs).

Results: Compared to placebo, a single daily dose of R-AMPH significantly improved SKAMP-Combined scores (p<0.0001) at each time point tested throughout the laboratory classroom days, with effect onset 45 minutes postdose and extending through 10 hours. R-AMPH significantly improved PERMP number of problems attempted and correct (p<0.0001) throughout the laboratory classroom days. During the twice-daily dose-optimization open-label phase, improvements were observed with R-AMPH in scores of the ADHD-Rating Scale IV and Clinical Global Impressions Severity and Improvement Scales. TEAEs and changes in vital signs associated with R-AMPH were generally mild and not unexpected. The most common TEAEs in the open-label phase were decreased appetite (27.6%), upper abdominal pain (14.3%), irritability (14.3%), and headache (13.3%).

Conclusions: Compared to placebo, R-AMPH was effective in treating children aged 6-12 years with ADHD, beginning at 45 minutes and continuing through 10 hours postdose, and was well tolerated.

Trial registration: ClinicalTrials.gov identifier: NCT01986062. https://clinicaltrials.gov/ct2/show/NCT01986062.

No MeSH data available.


Related in: MedlinePlus

Laboratory classroom SKAMP-Combined scores. SKAMP, Swanson, Kotkin, Agler, M-Flynn, and Pelham.
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f3: Laboratory classroom SKAMP-Combined scores. SKAMP, Swanson, Kotkin, Agler, M-Flynn, and Pelham.

Mentions: Figure 3 shows the SKAMP-Combined scores over the course of the 2 laboratory classroom days—during which, overall, each subject received R-AMPH and placebo. Significant separation from placebo occurred at each time point tested (0.75, 2, 4, 6, 8, and 10 hours) (p<0.0001 for all time points), with onset of R-AMPH effect by 45 minutes postdose (difference in LS means of −5.5 points) and with the greatest R-AMPH effect seen at 4 hours postdose (difference in LS means of −8.3 points). R-AMPH was still effective at 10 hours postdose (difference in LS means of −4.3 points), the last time point measured. The duration of the R-AMPH effect was therefore at least 9.25 hours (from 0.75 hours to the end of the study at 10 hours). Statistically significant differences (p<0.0001) in LS means for the change from predose SKAMP-Combined scores also favored R-AMPH treatment compared to placebo at each postdose time point, with the greatest change from baseline in R-AMPH treatment occurring at 2 hours postdose. When postdose SKAMP-Combined scores were analyzed by clinical site for the ITT population, the differences in LS means favored R-AMPH treatment at all time points for all sites. When SKAMP-Combined scores were examined across different subgroups (final dose, subject age, gender, race, ADHD type), statistically significant differences in LS means favoring R-AMPH treatment over placebo were observed at each time point through 10 hours postdose, with results similar to those for the ITT population as a whole.


The Efficacy and Safety of Evekeo, Racemic Amphetamine Sulfate, for Treatment of Attention-Deficit/Hyperactivity Disorder Symptoms: A Multicenter, Dose-Optimized, Double-Blind, Randomized, Placebo-Controlled Crossover Laboratory Classroom Study.

Childress AC, Brams M, Cutler AJ, Kollins SH, Northcutt J, Padilla A, Turnbow JM - J Child Adolesc Psychopharmacol (2015)

Laboratory classroom SKAMP-Combined scores. SKAMP, Swanson, Kotkin, Agler, M-Flynn, and Pelham.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4491157&req=5

f3: Laboratory classroom SKAMP-Combined scores. SKAMP, Swanson, Kotkin, Agler, M-Flynn, and Pelham.
Mentions: Figure 3 shows the SKAMP-Combined scores over the course of the 2 laboratory classroom days—during which, overall, each subject received R-AMPH and placebo. Significant separation from placebo occurred at each time point tested (0.75, 2, 4, 6, 8, and 10 hours) (p<0.0001 for all time points), with onset of R-AMPH effect by 45 minutes postdose (difference in LS means of −5.5 points) and with the greatest R-AMPH effect seen at 4 hours postdose (difference in LS means of −8.3 points). R-AMPH was still effective at 10 hours postdose (difference in LS means of −4.3 points), the last time point measured. The duration of the R-AMPH effect was therefore at least 9.25 hours (from 0.75 hours to the end of the study at 10 hours). Statistically significant differences (p<0.0001) in LS means for the change from predose SKAMP-Combined scores also favored R-AMPH treatment compared to placebo at each postdose time point, with the greatest change from baseline in R-AMPH treatment occurring at 2 hours postdose. When postdose SKAMP-Combined scores were analyzed by clinical site for the ITT population, the differences in LS means favored R-AMPH treatment at all time points for all sites. When SKAMP-Combined scores were examined across different subgroups (final dose, subject age, gender, race, ADHD type), statistically significant differences in LS means favoring R-AMPH treatment over placebo were observed at each time point through 10 hours postdose, with results similar to those for the ITT population as a whole.

Bottom Line: Compared to placebo, a single daily dose of R-AMPH significantly improved SKAMP-Combined scores (p<0.0001) at each time point tested throughout the laboratory classroom days, with effect onset 45 minutes postdose and extending through 10 hours.R-AMPH significantly improved PERMP number of problems attempted and correct (p<0.0001) throughout the laboratory classroom days.TEAEs and changes in vital signs associated with R-AMPH were generally mild and not unexpected.

View Article: PubMed Central - PubMed

Affiliation: 1 Center for Psychiatry and Behavioral Medicine , Las Vegas, Nevada.

ABSTRACT

Objective: The study goal was to determine the efficacy and safety of an optimal dose of Evekeo, racemic amphetamine sulfate, 1:1 d-amphetamine and l-amphetamine (R-AMPH), compared to placebo in treating children with attention-deficit/hyperactivity disorder (ADHD) in a laboratory classroom setting.

Methods: A total of 107 children ages 6-12 years were enrolled in this multicenter, dose-optimized, randomized, double-blind, placebo-controlled crossover study. After 8 weeks of open-label dose optimization, 97 subjects were randomized to 2 weeks of double-blind treatment in the sequence of R-AMPH followed by placebo (n=47) or placebo followed by R-AMPH (n=50). Efficacy measures included the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale and Permanent Product Measure of Performance (PERMP) administered predose and at 0.75, 2, 4, 6, 8, and 10 hours postdose on 2 laboratory classroom days. Safety assessments included physical examination, chemistry, hematology, vital signs, and treatment-emergent adverse events (TEAEs).

Results: Compared to placebo, a single daily dose of R-AMPH significantly improved SKAMP-Combined scores (p<0.0001) at each time point tested throughout the laboratory classroom days, with effect onset 45 minutes postdose and extending through 10 hours. R-AMPH significantly improved PERMP number of problems attempted and correct (p<0.0001) throughout the laboratory classroom days. During the twice-daily dose-optimization open-label phase, improvements were observed with R-AMPH in scores of the ADHD-Rating Scale IV and Clinical Global Impressions Severity and Improvement Scales. TEAEs and changes in vital signs associated with R-AMPH were generally mild and not unexpected. The most common TEAEs in the open-label phase were decreased appetite (27.6%), upper abdominal pain (14.3%), irritability (14.3%), and headache (13.3%).

Conclusions: Compared to placebo, R-AMPH was effective in treating children aged 6-12 years with ADHD, beginning at 45 minutes and continuing through 10 hours postdose, and was well tolerated.

Trial registration: ClinicalTrials.gov identifier: NCT01986062. https://clinicaltrials.gov/ct2/show/NCT01986062.

No MeSH data available.


Related in: MedlinePlus