Efficacy and Safety of a Long-Acting Multilayer-Release Methylphenidate Formulation (PRC-063) in the Treatment of Adolescent Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind Clinical Trial with a 6-Month Open-Label Extension
Bibliographic record
Abstract
Objectives: To study the safety and efficacy of the long-acting methylphenidate formulation PRC-063 in adolescents with attention-deficit/hyperactivity disorder (ADHD). Methods: Adolescents 12 to ≤17 years who met Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for ADHD and had a baseline ADHD Rating Scale DSM-5 (ADHD-5-RS) score ≥24 participated in a randomized, double-blind, placebo-controlled, fixed-dose, parallel-group study. Participants were randomized 1:1:1:1:1 to receive placebo or one of four doses of PRC-063 once daily for 4 weeks. The primary endpoint was change from baseline in least-squares mean clinician-rated ADHD-5-RS total score for PRC-063 (all doses combined) versus placebo. Other efficacy assessments included Conners third Edition: Self-Report (C3SR) and Clinical Global Impression-Improvement (CGI-I). A subset of double-blind study participants entered a subsequent open-label, dose-optimized study. Safety outcomes in both studies included treatment-emergent adverse events (TEAEs). Results: Three hundred fifty-four participants were included in the primary analysis. The least-squares mean change from baseline in ADHD-5-RS total score was −15.17 for PRC-063 versus −10.98 for placebo (least-squares mean difference −4.2, p = 0.0067). For individual PRC-063 doses, improvements in ADHD-5-RS total score versus placebo were significant for 45 mg ( p = 0.0155) and 70 mg ( p = 0.0401), but not for 25 or 85 mg. A significant improvement for PRC-063 versus placebo was recorded for C3SR Inattention ( p = 0.0168), but not for the other C3SR subscales. About 52.7% of participants randomized to PRC-063 were responders based on CGI-I versus 32.4% of those randomized to placebo ( p = 0.0004). Further improvements in ADHD symptoms based on ADHD-5-RS were observed from 1 month through 6 months of open-label treatment ( p < 0.0001). There were two serious adverse events (both during the open-label study), one of which (aggressive behavior) was assessed as related to study drug. The only TEAEs that occurred in >10% of participants during double-blind treatment were decreased appetite (20.1%) and headache (15.0%). Most TEAEs were of mild or moderate severity. Conclusion: PRC-063 significantly improved ADHD symptomatology in adolescents. It was generally well tolerated, with an AE profile consistent with other long-acting stimulants. NCT02139111 and NCT02168127.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".