New CTx-1301 Data Affirms Pharmacokinetic Profile to Treat ADHD

Developers of CTx-1301, Cingulate, have published positive results in CNS Drugs on pharmacokinetics of the trimodal dexmethylphenidate HCl formulation to treat attention-deficit hyperactive disorder (ADHD).^1,2 The paper follows recent positive phase 3 efficacy and safety results, adding evidence for unique pharmacokinetic characteristics of CTx-1301.³

"As a clinician, I look closely at how a stimulant medication is delivered over the course of a patient’s active day because that helps us understand its pharmacokinetic profile," said Ann Childress, MD, lead investigator for Cingulate's phase 3 efficacy and safety trial. "This study demonstrates that CTx-1301 was designed as a true once-daily medication, delivering 3 distinct releases of dexmethylphenidate that create a pharmacokinetic profile different from currently available stimulant formulations. These data help clinicians better understand the science behind the formulation and how it was designed to provide medication exposure throughout the active day," she added.

The paper compared bioavailability of the trimodal CTx-101 vs bimodal dexmethylphenidate modified-release formulations in adults with ADHD. In a randomized, 4-period crossover study, 45 participants received single doses of CTx-1301 (50 mg and 6.25 mg) or the bimodal comparator formulation (40 mg and 5 mg). Bioavailability was assessed through adjusted geometric mean ratios for exposure parameters (maximum observed plasma concentration, area under plasma concentration-time curve (AUC) to last measurable concentration). Secondary measurements included partial AUCs and safety assessments. Participants were predominantly White (55.6%) and male (88.9%) with a mean age of 29.6.

Key exposure parameters for trimodal CTx-1301 were statistically bioequivalent to the bimodal comparison. Early exposure was rapid compared to the reference drug, and significantly higher dexmethylphenidate concentrations were found in later hours of the dosing interval. Plasma drug concentration decline was controlled, reducing late-day wearing off effects. CTx-1301 was shown to be generally well-tolerated, with most commonly reported adverse events of tachycardia, insomnia, headache, nausea, and euphoric mood. Incidence of treatment-emergent adverse events was numerically lower with CTx-1301 than the bimodal comparison formulation, but no statistical analysis was performed. The drug demonstrated dose proportionality and was tolerated at high and low doses.

"With the publication of our Phase 3 efficacy study followed now by this pharmacokinetic analysis, we have established a peer-reviewed scientific foundation for CTx-1301," stated Cingulate chairman and chief executive officer Shane J. Schaffer, PharmD. "Together, these publications help explain both the clinical performance observed in the Phase 3 study and the proprietary technology designed to support CTx-1301's delivery profile."

CTx-1301 is a once-daily, multi-core dexmethylphenidate HCl formulation. The drug uses Precision Timed Release technology to deliver 3 precisely timed doses of active medication throughout the day; release timing aims to provide rapid onset of effect and entire active-day duration. The multi-core delivery includes a proprietary erosion barrier layer, providing drug release at specified times with a tablet-in-tablet dose form.

The medication previously received a Complete Response Letter from the FDA in June 2026, but issues were based in information about chemistry, manufacturing, and controls, rather than safety or efficacy.⁴ CTx-1301 is currently being evaluated for treatment of ADHD under the US Food and Drug Administration 505(b)(2) pathway.

References

1. Cingulate publishes peer-reviewed data demonstrating CTx-1301’s differentiated pharmacokinetic profile. Press release. August 11, 2026. Accessed August 11, 2026. https://www.biospace.com/press-releases/cingulate-publishes-peer-reviewed-data-demonstrating-ctx-1301s-differentiated-pharmacokinetic-profile

2. Straughn AB, Silva R, Cattaneo MJ, et al. Comparative bioavailability of trimodal (CTx-1301) versus bimodal dexmethylphenidate modified-release formulations in adults with attention-deficit/hyperactivity disorder: a randomized, single-dose, crossover study. CNS Drugs. 2026.

3. Childress A, Brams M, Cattaneo MJ, et al. Efficacy and safety of trimodal dexmethylphenidate (CTx-1301) in children and adolescents with attention-deficit/hyperactivity disorder: results from a phase 3, randomized, double-blind, fixed-dose, placebo-controlled trial. J Child Adolesc Psychopharmacol. 2026:10445463261469764.

4. Walters J. FDA issues CRL for CTx-1301 for treatment of ADHD. Psychiatric Times. June 2, 2026. https://www.psychiatrictimes.com/view/fda-issues-crl-for-ctx-1301-for-treatment-of-adhd