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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

Mean (SD) CGI-S scores in the open-label phase of the study. The CGI-S classifies current disease state as follows: 1=normal, not at all ill; 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill subjects; CGI-S, Clinical Global Impressions–Severity.
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f7: Mean (SD) CGI-S scores in the open-label phase of the study. The CGI-S classifies current disease state as follows: 1=normal, not at all ill; 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill subjects; CGI-S, Clinical Global Impressions–Severity.

Mentions: At the screening visit, 49.5% of subjects were considered moderately ill, as rated by the CGI-S score of 4; 37.1% were considered markedly ill (CGI-S score of 5) and 10.3% were considered severely ill (CGI-S score of 6). Only 3.1% of subjects were considered mildly ill (CGI-S score of 3). By the end of the 8-week open-label phase, 33.0% of subjects were considered normal, not at all ill (CGI-S score of 1), 26.8% were borderline ill (CGI-S score of 2), 37.1% were mildly ill, 3.1% were moderately ill, and no subjects were classified as markedly or severely ill. Mean (SD) CGI-S scores decreased from 4.6 (0.70) at baseline to 2.1 (0.91) by the end of the open-label phase (Fig. 7). Based on the CGI-I measure of disease improvement relative to baseline, subjects continued to improve throughout the 8-week open-label phase. By week 4, 100% of subjects showed improvement (42.3% very much improved, 42.3% much improved, and 15.5% minimally improved). By week 8, 71.1% were very much improved, 23.7% were much improved, and 5.2% were minimally improved (Fig. 8). Mean (SD) CGI-I scores improved from 3.3 (0.94) at the end of open-label week 1 to 1.3 (0.58) at the end of open-label week 8.


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)

Mean (SD) CGI-S scores in the open-label phase of the study. The CGI-S classifies current disease state as follows: 1=normal, not at all ill; 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill subjects; CGI-S, Clinical Global Impressions–Severity.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f7: Mean (SD) CGI-S scores in the open-label phase of the study. The CGI-S classifies current disease state as follows: 1=normal, not at all ill; 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill subjects; CGI-S, Clinical Global Impressions–Severity.
Mentions: At the screening visit, 49.5% of subjects were considered moderately ill, as rated by the CGI-S score of 4; 37.1% were considered markedly ill (CGI-S score of 5) and 10.3% were considered severely ill (CGI-S score of 6). Only 3.1% of subjects were considered mildly ill (CGI-S score of 3). By the end of the 8-week open-label phase, 33.0% of subjects were considered normal, not at all ill (CGI-S score of 1), 26.8% were borderline ill (CGI-S score of 2), 37.1% were mildly ill, 3.1% were moderately ill, and no subjects were classified as markedly or severely ill. Mean (SD) CGI-S scores decreased from 4.6 (0.70) at baseline to 2.1 (0.91) by the end of the open-label phase (Fig. 7). Based on the CGI-I measure of disease improvement relative to baseline, subjects continued to improve throughout the 8-week open-label phase. By week 4, 100% of subjects showed improvement (42.3% very much improved, 42.3% much improved, and 15.5% minimally improved). By week 8, 71.1% were very much improved, 23.7% were much improved, and 5.2% were minimally improved (Fig. 8). Mean (SD) CGI-I scores improved from 3.3 (0.94) at the end of open-label week 1 to 1.3 (0.58) at the end of open-label week 8.

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