ObjectiveThe objective of this randomized, double-blind, placebo-controlled study was to evaluate the efficacy and safety of SHP465 mixed amphetamine salts (MAS) in adults with attention-deficit/hyperactivity disorder (ADHD).MethodsEligible adults [aged 18–55 years; meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ADHD criteria; baseline ADHD Rating Scale with Adult Prompts (ADHD-RS-AP) total scores ≥28] were randomized 1:1:1 to placebo or forced-dose SHP465 MAS (12.5 or 37.5 mg/day) for 4 weeks. The ADHD-RS-AP total score change from baseline to week 4 (primary endpoint) and Clinical Global Impressions-Improvement score at week 4 (key secondary endpoint) were assessed using linear mixed-effects models for repeated measures. Other efficacy endpoints were changes from baseline to week 4 on the ADHD-RS-AP hyperactivity/impulsivity and inattentiveness subscales and the percentage of participants categorized as improved on the dichotomized Clinical Global Impressions-Improvement. Safety and tolerability assessments were treatment-emergent adverse events, vital sign and weight changes, Columbia-Suicide Severity Rating Scale responses, and electrocardiogram results.ResultsOf 369 screened participants, 275 were randomized (placebo, n = 91; 12.5 mg/day of SHP465 MAS, n = 92; 37.5 mg/day of SHP465 MAS, n = 92) and 236 completed the study (placebo, n = 80; 12.5 mg/day of SHP465 MAS, n = 80; 37.5 mg/day of SHP465 MAS, n = 76). Least-squares mean (95% confidence interval) treatment differences at week 4 significantly favored SHP465 MAS over placebo for the ADHD-RS-AP total score change from baseline [12.5 mg/day: −8.1 (−11.7, −4.4), effect size = 0.67; 37.5 mg/day: −13.4 (−17.1, −9.7), effect size = 1.11; both p < 0.001] and Clinical Global Impressions-Improvement score [12.5 mg/day: −0.8 (−1.1, −0.4), effect size = 0.68; 37.5 mg/day: −1.2 (−1.6, −0.9), effect size = 1.11; both p < 0.001]. Treatment differences for the change from baseline at week 4 favored 12.5 and 37.5 mg/day of SHP465 MAS, respectively, over placebo on the ADHD-RS-AP hyperactivity/impulsivity (both nominal p < 0.001; effect size = 0.56 and 0.91) and inattentiveness (both nominal p < 0.001; effect size = 0.70 and 1.19) subscales. At the final on-treatment assessment, the percentage of participants categorized as improved on Clinical Global Impressions-Improvement was higher with both SHP465 MAS doses than with placebo (both nominal p < 0.001). Treatment-emergent adverse events reported (>5%) with SHP465 MAS were decreased appetite, dry mouth, insomnia, headache, anxiety, initial insomnia, irritability, and bruxism. Severe treatment-emergent adverse events and treatment-emergent adverse events leading to discontinuation, respectively, were reported by 8 and 12 participants (placebo, n = 2 and 0; 12.5 mg/day SHP465 MAS, n = 1 and 7; 37.5 mg/day SHP465 MAS, n = 5 and 5). At the final on-treatment assessment, mean ± standard deviation increases from baseline were observed with 12.5 and 37.5 mg/day of SHP465 MAS for pulse (3.3 ± ...
Modafinil was reasonably tolerated but did not demonstrate a benefit on ADHD symptoms in adults.
Once-daily treatment with LDX was associated with significant improvement in parent-rated assessments of ADHD-related behavior throughout the day at approximately 10:00 AM, 2:00 PM, and 6:00 PM. Lisdexamfetamine dimesylate was effective and well tolerated in this study population of children aged 6 to 12 years with ADHD.
ImportanceGreater than 20% of cases and 0.4% of deaths from COVID-19 occur in children. Following demonstration of the safety and efficacy of the adjuvanted, recombinant spike protein vaccine NVX-CoV2373 in adults, the PREVENT-19 trial immediately expanded to adolescents.ObjectiveTo evaluate the safety, immunogenicity, and efficacy of NVX-CoV2373 in adolescents.Design, Setting, and ParticipantsThe NVX-CoV2373 vaccine was evaluated in adolescents aged 12 to 17 years in an expansion of PREVENT-19, a phase 3, randomized, observer-blinded, placebo-controlled multicenter clinical trial in the US. Participants were enrolled from April 26 to June 5, 2021, and the study is ongoing. A blinded crossover was implemented after 2 months of safety follow-up to offer active vaccine to all participants. Key exclusion criteria included known previous laboratory-confirmed SARS-CoV-2 infection or known immunosuppression. Of 2304 participants assessed for eligibility, 57 were excluded and 2247 were randomized.InterventionsParticipants were randomized 2:1 to 2 intramuscular injections of NVX-CoV2373 or placebo, 21 days apart.Main Outcomes and MeasuresSerologic noninferiority of neutralizing antibody responses compared with those in young adults (aged 18-25 years) in PREVENT-19, protective efficacy against laboratory-confirmed COVID-19, and assessment of reactogenicity and safety.ResultsAmong 2232 participants (1487 NVX-CoV2373 and 745 placebo recipients), the mean (SD) age was 13.8 (1.4) years, 1172 (52.5%) were male, 1660 (74.4%) were White individuals, and 359 (16.1%) had had a previous SARS-CoV-2 infection at baseline. After vaccination, the ratio of neutralizing antibody geometric mean titers in adolescents compared with those in young adults was 1.5 (95% CI, 1.3-1.7). Twenty mild COVID-19 cases occurred after a median of 64 (IQR, 57-69) days of follow-up, including 6 among NVX-CoV2373 recipients (incidence, 2.90 [95% CI, 1.31-6.46] cases per 100 person-years) and 14 among placebo recipients (incidence, 14.20 [95% CI, 8.42-23.93] cases per 100 person-years), yielding a vaccine efficacy of 79.5% (95% CI, 46.8%-92.1%). Vaccine efficacy for the Delta variant (the only viral variant identified by sequencing [n = 11]) was 82.0% (95% CI, 32.4%-95.2%). Reactogenicity was largely mild to moderate and transient, with a trend toward greater frequency after the second dose of NVX-CoV2373. Serious adverse events were rare and balanced between treatments. No adverse events led to study discontinuation.Conclusions and RelevanceThe findings of this randomized clinical trial indicate that NVX-CoV2373 is safe, immunogenic, and efficacious in preventing COVID-19, including the predominant Delta variant, in adolescents.Trial RegistrationClinicalTrials.gov Identifier: NCT04611802
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