Comparative Bioavailability of Trimodal (CTx-1301) Versus Bimodal Dexmethylphenidate Modified-Release Formulations in...

Area of Science:

• Pharmacokinetics
• Pharmacology
• Neuroscience

Background:

• Attention-deficit/hyperactivity disorder (ADHD) requires sustained symptom management.
• Bimodal extended-release dexmethylphenidate (d-MPH XR) may not provide consistent late-day therapeutic exposure.
• Trimodal formulations offer a potential for extended drug release into the evening.

Purpose of the Study:

• To compare the pharmacokinetic (PK) profiles of a trimodal formulation (CTx-1301) and a bimodal formulation (d-MPH XR) of dexmethylphenidate.
• To assess the bioavailability of CTx-1301 and d-MPH XR at high and low doses.
• To evaluate the potential for extended drug release with the trimodal formulation.

Main Methods:

• A randomized, 4-period, crossover study in adults with ADHD.
• Single doses of CTx-1301 (50 mg and 6.25 mg) and d-MPH XR (40 mg and 5 mg) were administered.
• Comparative bioavailability was assessed using adjusted geometric mean ratios for Cmax, AUC(last), and AUC(0-inf) within a bioequivalence range of 0.80-1.25.

Main Results:

• Key exposure parameters (Cmax, AUC(last), AUC(0-inf)) for CTx-1301 were bioequivalent to d-MPH XR at both high and low doses.
• Partial AUC analyses showed CTx-1301 had higher exposure during later post-dose intervals (9-16 h).
• Dose proportionality was observed for both formulations; CTx-1301 was generally well tolerated.

Conclusions:

• Trimodal CTx-1301 is statistically bioequivalent to bimodal d-MPH XR regarding key exposure parameters.
• CTx-1301 demonstrates extended drug release in later post-dose intervals, consistent with its formulation.
• Further evaluation is needed to determine the clinical relevance of these PK differences.