Clinicians rated 82% of the patients receiving the study drug and 46% in the placebo group as either much improved or very much improved on the Clinical Global Impression of Improvement scale.
Ann C. Childress, MD
A common issues for patients suffering from attention deficit/hyperactivity disorder (ADHD) is that medication can wane over the course of the day in effectiveness.
A team, led by Ann C. Childress, Center for Psychiatry and Behavioral Medicine, assessed the clinical efficacy, time to onset and duration of efficacy, and safety of PRC-063 compared to placebo in adult ADHD patients.
Adults who suffer from ADHD commonly suffer from inattentiveness, a lack of focus, impulsivity, and excessive physical activity. While methylphenidate is a prescribed drug showing efficacy in managing ADHD, because of rapid absorption and a short half-life, the clinical effects of immediate release methylphenidate last for only about 4 hours.
This makes a multiple daily dose of the immediate release formulation or in combination with an extended-release formulation would be necessary in some patients to treat their symptoms throughout the day.
PRC-063 is an extended-release formulation designed specifically to provide sustained delivery for patients with ADHD who require symptom control throughout the day. The multilayer-release beaded formulation enables the patient to take 1 pill daily in the morning. Each identical PRC-063 bead contains both an immediate-release component that represents about 20% of the total dose and a controlled-release component that represents about 80% of the total dose.
In the randomized, double-blind, parallel-group, placebo-controlled, dose-optimized, phase 3 trial, the investigators examined 288 patients who met the inclusion criteria of Structured Clinical Interview for DSM-5 (SCID-5) diagnosis of any of the 3 subtypes of ADHD, ADHD Rating Scale IV (ADHD-RSIV) score ≥28 at baseline, not receiving or dissatisfied with current ADHD therapy, or treatment-naïve, and able to complete standardized, skill-adjusted math tests.
Of the original 288 patients, 239 individuals entered the double-blind period and 221 completed the full-day ALC visit. The median age of the participants was 31 years old, while 54.7% were female. The majority of patients (83.9%) had combined type ADHD and disease severity based on ADHD-RS-IV total scores at baseline were moderate (37.5%) or severe (62.5%).
Following a 7 week dose optimization period, 113 patients were randomized to placebo and 116 patients were randomized to PRC-063.
Following a half-day ALC visit, eligible patients were randomized to receive either the study drug or a placebo for 1 week. The researchers then evaluated post-dose standardized, skill-adjusted math test total scores during the full-day ALC visit.
They also evaluated prespecified safety endpoints throughout the dose-optimization and double-blind treatment periods.
Each participant kept a daily diary to record detail of their sleep during the washout, dose-optimization, and double-blind treatment periods.
Ultimately, the study drug met the primary endpoint of improved post-dose math test total scores across all timepoints during the ALC (least-squares mean difference [SE], 16.3 [4.39]; P = 0.0003).
The researchers also met their secondary endpoints, including improved post-dose math test total scores compared to placebo at every post-dose time point beginning at 1 hour up to and including 16 hours (P < 0.05). During the full-day ALC, the investigators found the PRC-063 group achieved improved ADHD-RS-IV scores when compared to placebo (-8.5 [1.41]; P <0.0001).
In addition, during the full-day ALC, clinicians rated 82% of the patients receiving the study drug and 46% in the placebo group as either much improved or very much improved on the Clinical Global Impression of Improvement (CGI-I) scale.
They also found 78% of the subjects receiving PRC-063 and 42% receiving the placebo as non-severe.
During the dose-optimization period, headaches, decreased appetite, and clinically defined inability to sleep were treatment-emerge adverse events that occurred most frequently. The TEAEs that occurred in at least 2% of both study arms were headaches, fatigue, and upper respiratory tract infections.
“In this ALC study, PRC-063 was well-tolerated and effective for the treatment of ADHD in adults, with onset of action at 1 hour and duration of effect up to and including 16 hours post-dose,” the authors wrote.
The study, “Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Adult Laboratory Classroom Study to Evaluate the Safety and Efficacy of PRC-063 Compared with Placebo for the Treatment of ADHD,” was published online by NEI.