FDA Issues CRL for CTx-1301 for Treatment of ADHD

The US Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) in response to the New Drug Application (NDA) for CTx-1301, a novel formulation of dexmethylphenidate for treatment of attention-deficit hyperactivity disorder (ADHD).¹ The FDA’s letter requested specific information about chemistry, manufacturing, and controls, without raising concerns about safety or efficacy of the medication.

“We are encouraged that the FDA’s response was limited to specific information requests related to [chemistry, manufacturing, and controls] and did not currently identify any issues related to the clinical safety or efficacy of CTx-1301,” said Shane J. Schaffer, Cingulate’s chief executive officer. “Our immediate priority is to complete the [chemistry, manufacturing, and controls] work already underway with our manufacturing partner; we believe the outstanding requests will be addressed quickly as we move efficiently toward resubmission,” he added.

Previous positive phase 3 data has been published in multiple age groups, from a dose-optimization study in adults and 2 further phase 3 adolescent studies.² The randomized, double-blind, placebo-controlled study in children and adolescents met its primary endpoint of dose-dependent improvements on the ADHD Rating Scale 5 and the Clinical Global Impression-Severity scale, showing rapid onset and sustained efficacy throughout the day. CTx-1301 also had a lower incidence of treatment-related adverse events (9%) compared with placebo (30%), indicating a positive safety profile.³

Cingulate submitted a New Drug Application (NDA) for CTx-1301 to the FDA in July 2025 and received approval in October 2025, which set the FDA action date for the end of May 2026, culminating in issuance of the CRL in early June.⁴ CTx-1301 was reviewed via the FDA 505(b)(2) regulatory pathway, a path that allows reference to existing data on previously approved active ingredients while demonstrating novel clinical benefit through a differentiated delivery mechanism.

“CTx-1301 was engineered to address the practical shortcomings of today’s stimulant therapies—multiple daily dosing, midday rebound, and adherence challenges—through a single, once-daily tablet,” said Cingulate’s executive chairman, Jay Roberts, in a press release when the NDA was accepted.

The drug uses a proprietary timed-release formula developed by Cingulate to provide 3 different timings of medication dosage throughout the day.⁵ CTx-1301 is designed to deliver 3 separate releases with one tablet, giving both rapid onset and entire-day efficacy. An erosion barrier layer provides the ability for specifically timed release of the drug.⁶ This technology fulfills an unmet need for a longer-acting dose with a single pill, as the third dose is released around the time where other extended-release medications wear off.

Cingulate noted plans to share requested information addressing issues raised with the FDA promptly.

References

1. Cingulate receives Complete Response Letter from FDA for CTx-1301. Press release. Accessed June 2, 2026. https://finance.yahoo.com/sectors/healthcare/articles/cingulate-receives-complete-response-letter-120000413.html

2. Kuntz L. Positive phase 3 results: CTx-1301 for the treatment of pediatric ADHD. Psychiatric Times. October 28, 2025. https://www.psychiatrictimes.com/view/positive-phase-3-results-ctx-1301-for-the-treatment-of-pediatric-adhd

3. Childress A, Brams M, Koehn K, et al. A phase 3, dose-optimized, double-blind, randomized, placebo controlled, single-center, parallel efficacy and safety laboratory classroom study in adults with attention-deficit/hyperactivity disorder (ADHD) using CTx-1301 (dexmethylphenidate): effect size assessment. American Professional Society of ADHD and Related Disorders (APSARD) Annual Meeting. Poster presentation. Accessed May 28, 2026. https://www.cingulate.com/static-files/b3c901ad-8d47-4ebc-b0a8-41c7330bc1b6

4. Kuntz L. FDA accepts NDA for CTx-1301 for treatment of ADHD. Psychiatric Times. October 14, 2025. https://www.psychiatrictimes.com/view/fda-accepts-nda-for-ctx-1301-for-treatment-of-adhd

5. CTx-1301. Cingulate. Accessed June 2, 2026. https://www.cingulate.com/pipeline/ctx-1301 

6. Cingulate submits New Drug Application to FDA for lead ADHD asset CTx-1301. Press release. August 7, 2025. Accessed May 28, 2026. https://www.biospace.com/press-releases/cingulate-submits-new-drug-application-to-fda-for-lead-adhd-asset-ctx-1301