Delving into the Latest Updates on Centanafadine Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Centanafadine, Centanafadine hydrochloride (USAN), Centanafadine SR

+ [10]

Target

DAT x NET x SERT

Action

inhibitors

Mechanism

Dopamine reuptake inhibitors, NET inhibitors(Norepinephrine transporter inhibitors), Serotonin reuptake inhibitors

Therapeutic Areas

Other DiseasesNervous System Diseases

Active Indication

Generalized anxiety disorderAttention Deficit Disorder With HyperactivityDepressive Disorder, Major

Inactive Indication

Attention Deficit DisorderBinge-Eating DisorderSmoking Cessation

Originator Organization

Euthymics Bioscience, Inc.

Active Organization

Otsuka Pharmaceutical Co., Ltd.Otsuka Pharmaceutical Development & Commercialization, Inc.

Otsuka Holdings Co., Ltd.

Inactive Organization

Neurovance, Inc.

License Organization-

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC15H16ClN

InChIKeyACVMJAJGCQUPKX-LIOBNPLQSA-N

CAS Registry923981-14-0

To compare the short-term safety and efficacy of centanafadine, an investigational treatment, versus long-acting controlled-release methylphenidate hydrochloride (methylphenidate, Foquest ® ) among adult patients with attention-deficit/hyperactivity disorder (ADHD), using matching-adjusted indirect comparison (MAIC).

Methods:

This anchored MAIC used pooled individual patient data (IPD) from two centanafadine trials (NCT03605680, NCT03605836) and published aggregate data from one methylphenidate trial (NCT02139124). Using propensity scores, IPD from the centanafadine trials were reweighted to match the aggregate baseline characteristics of the methylphenidate trial. Safety and efficacy outcomes were compared at Week 4. Safety outcomes were the rates of adverse events reported by ≥5% of patients in any treatment group in either trial with an incidence twice that of the placebo. The efficacy outcome was the mean change from baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS)/ADHD Rating Scale–5 (ADHD-RS-5) score at Week 4.

Results:

After matching, no significant differences in baseline characteristics were observed across trials. Relative to methylphenidate, centanafadine exhibited a better safety profile, with a significantly lower risk of insomnia (risk difference in percentage points: −9.46 points) and initial insomnia (−4.68 points). There was no significant difference in efficacy across treatments as measured by the mean change from baseline in AISRS/ADHD-RS-5 score.

Conclusions:

In this MAIC, centanafadine was associated with a lower risk of insomnia and comparable (i.e., nondifferent) efficacy compared to methylphenidate at Week 4. Information on the comparative safety and efficacy of ADHD treatments in the adult population will help inform personalized treatment decisions given the range of treatment options with varying attributes.

01 Jul 2025·JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY

Centanafadine for Attention-Deficit/Hyperactivity Disorder in Adolescents: A Randomized Clinical Trial

Article

Author: Ward, Caroline L ; Wilens, Timothy E ; Turkoglu, Osman ; Jin, Na ; Childress, Ann C ; Skubiak, Taisa

OBJECTIVE:

This randomized, double-blind, placebo-controlled trial evaluated the efficacy, safety, and tolerability of centanafadine-a norepinephrine, dopamine, serotonin reuptake inhibitor-in the treatment of attention-deficit/hyperactivity disorder (ADHD) in adolescents.

METHOD:

Adolescents (aged 13-17 years, inclusive) with a primary diagnosis of ADHD were randomized to once-daily centanafadine 164.4 mg, 328.8 mg, or placebo for 6 weeks. Dosing was not titrated. The primary endpoint was change from baseline in the ADHD Rating Scale, version 5 (ADHD-RS-5) symptoms total raw score at week 6. This trial is registered with ClinicalTrials.gov (NCT05257265).

RESULTS:

Of 459 participants (centanafadine 164.4 mg, n = 155; 328.8 mg, n = 155; placebo, n = 149), 451 received ≥1 dose of study drug and 371 (80.8%) completed the trial. At week 6, improvements in ADHD-RS-5 symptoms total raw score were significantly greater with centanafadine 328.8 mg than with placebo (-18.50 [0.93] vs -14.15 [0.93]; p = .0006); centanafadine 164.4 mg did not meet the primary endpoint. Centanafadine 328.8 mg showed separation from placebo at week 1, the first postbaseline timepoint, with the effect maintained throughout the study. Treatment-emergent adverse events (TEAEs) occurred in 48 of 153 (31.4%, 164.4 mg), 76 of 151 (50.3%, 328.8 mg), and 35 of 147 (23.8%, placebo) participants. The most common (≥5% any group) TEAEs were decreased appetite, nausea, headache, and rash. Most TEAEs were of mild or moderate severity; 3 events were severe: liver function test increase (n = 1, 164.4 mg); aggression (n = 1, 164.4 mg); and somnolence (n = 1, placebo).

CONCLUSION:

Centanafadine 328.8 mg was efficacious for ADHD treatment in adolescents. Both doses were generally safe and well tolerated.

CLINICAL TRIAL REGISTRATION INFORMATION:

A Trial of Centanafadine Efficacy and Safety in Adolescents With Attention-Deficit/Hyperactivity Disorder; https://clinicaltrials.gov/study/NCT05257265 DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper self-identifies as living with a disability. We actively worked to promote sex and gender balance in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

01 Feb 2025·Contemporary Clinical Trials Communications

Conducting clinical trials with self-collection of pharmacokinetic samples: Experience from an exploratory, phase 1, open-label trial of centanafadine SR in healthy individuals

Article

Author: Bullock, Michelle ; Shoaf, Susan E ; Shablinski, Tatiana ; Chung, Chris ; Ye, Chelsea

Background:

The COVID-19 pandemic accelerated a shift to decentralized clinical trials. We present the potential feasibility of this approach from a phase 1 pharmacokinetic (PK) trial.

Methods:

Healthy adults (18-55 years) with a body mass index of 19.0-32.0 kg/m² were enrolled. The trial comprised a screening period, 2 clinic visits (visits 1, 2), 2 at-home visits (visits 3 and 4), and follow-up clinic visit (visit 5). Participants received a single 100-mg oral dose of centanafadine sustained release at visits 1, 2, and 4. Pharmacokinetic samples, electrocardiograms (ECGs; 6-lead [participant] and 12-lead [staff]), and vital signs were collected by clinical personnel (visit 1), under staff supervision (visit 2), and remotely (visit 4), facilitated by the Verily clinical trial application. Successful sample collection at visit 4 was reported descriptively. A survey assessed the utility of training, devices, and the Verily app, and ability to complete trial procedures.

Results:

Among 20 participants enrolled, 90 % were female, mean (SD) age was 35.9 (11.1) years. Verily platform/procedures facilitated successful remote vital sign collection in at least 75 %, ECGs in at least 80 %, and blood microsamples in 65 %-70 % of participants at visit 4. Most agreed that training was adequate, and they were able to complete trial procedures on their own. Participants favored self-collection over staff collection, having visits in their own location, and would consider participation in similar future research.

Conclusions:

Results from this decentralized PK trial, with remote, in-home sample collection and monitoring, demonstrated the potential feasibility of this study design.

7

News (Medical) associated with Centanafadine Hydrochloride

30 Jul 2024

·www.pharmaceutical-technology.com

Collegium buys Ironshore for $525m and enter ADHD market

Collegium will also pay an additional $25m if the sales of Ironshore’s Jornay PM exceed the defined revenue expectation in 2025. Image Credit: tomertu / Shutterstock. Collegium Pharmaceuticals has signed a definitive agreement to acquire Ironshore Therapeutics in a bid to expand its portfolio beyond pain management. Collegium will pay $525m in cash to acquire outstanding shares of Ironshore. Following the transaction, Collegium will gain Ironshore’s US Food and Drug Administration (FDA)-approved therapy, Jornay PM (methylphenidate hydrochloride), for treating attention deficit hyperactivity disorder (ADHD) in patients aged six years and older. The company will also pay an additional $25m if the sales of Jornay PM exceed Collegium’s defined revenue expectations in 2025. The deal is expected to close in Q3 this year. Concurrent with the acquisition, Collegium also secured $646m as part of a five-year loan from Pharmakon Advisors, which, along with Collegium’s cash reserves, will fund the Ironshore acquisition. “The Ironshore acquisition is a unique opportunity to deliver a transaction that is immediately accretive to Collegium while meeting all of our strategic objectives through the addition of a growing commercial asset that diversifies our portfolio, has significant revenue potential and exclusivity into the 2030s,” said Michael Heffernan, chairman and interim president and chief executive officer of Collegium. Whilst there is a significant unmet need for new ADHD therapeutics, simulant treatments like Jornay PM face significant disadvantages due to their abuse potential and their prescribed use being limited to 30 days. See Also: Pipeline power: Sionna’s AbbVie deal could redefine CF therapeutics Podcast #5: Doing Digital Deals in Life Sciences | Deal Structure, Terms, and Series Conclusions The current market leader in the ADHD space is Takeda with two FDA-approved treatments, Vyvanse (lisdexamfetamine dimesylate) and Intuniv (guanfacine hydrochloride). However, the overall market for ADHD therapeutics across seven major markets (US, France, Germany, Italy, Spain, UK, and Japan) is expected to decline to $10.9bn by 2032 from $11.9bn in 2022, as per GlobalData analysis. This is mainly driven by the launch and uptake of generics. GlobalData is the parent company of Pharmaceutical Technology . Late-stage ADHD therapies in development include Otsuka Pharmaceuticals’ non-stimulant therapy centanafadine and Cingulate’s CTx-1301 (dexmethylphenidate) , a once-daily stimulant therapy. In October 2023, Otsuka reported positive data from two Phase III trials showing centanafadine’s efficacy in treating ADHD in adolescents and children.

Clinical ResultPhase 3AcquisitionDrug Approval

30 Oct 2023

·www.biospace.com

Otsuka’s Centanafadine Shows Promise in Phase III Pediatric ADHD Studies

Pictured: Girl student having trouble concentratin The Japanese pharma’s attention deficit/hyperactivity disorder candidate has shown significant symptom improvements in children and adolescents in two late-stage studies. Pictured: Girl student having trouble concentrating/iStock, PeopleImages Otsuka Pharmaceutical on Friday posted top-line data from two Phase III studies, demonstrating that its attention deficit/hyperactivity disorder candidate centanafadine significantly improves symptoms in children and teenagers. Friday’s readouts come from attention deficit/hyperactivity disorder (ADHD) trials that are largely similar in design, employing three arms and fixed high or low doses of centanafadine which were given compared to placebo on a double-blinded basis. The main difference is in the study populations: one enrolled adolescent participants between the ages of 13 and 17 years, while the other included children aged six to 12 years. In the adolescent study, patients treated with high-dose centanafadine saw significantly better scores on the ADHD Rating Scale version 5 (ADHD-RS-5), a validated tool used to assess the severity of ADHD and the study’s primary endpoint. The average effect of both the high and low centanafadine doses was also significantly better than placebo. Centanafadine was similarly effective in children. ADHD-RS-5 scores significantly improved in patients who were treated with high-dose centanafadine, and the average treatment effect in both high-dose and low-dose groups was likewise statistically better than placebo. In the adolescent and pediatric trials, the benefits of high-dose centanafadine became apparent as early as the first post-baseline timepoint at week one, which was sustained for the rest of the study periods. However, both low-dose arms did not see significantly improved ADHD-RS-5 scores versus placebo. In terms of safety, pooling data from both studies demonstrated a tolerability pro was consistent with centanafadine’s broader clinical development program. The most common side effects included nausea, upper abdominal pain, somnolence and fatigue. While the full results from both studies are not yet available, these data “demonstrate centanafadine has the potential to offer a new treatment option for children and adolescents who live with ADHD,” John Kraus, chief medical officer of U.S. subsidiary Otsuka Pharmaceutical Development and Commercialization, said in a statement. Otsuka will submit complete data and analyses from both trials for scientific publication. The company will also use these findings, along with clinical pharmacology studies and long-term stability data, to build a New Drug Application for centanafadine in this indication. Friday’s ADHD readout comes months after Otsuka and partner Sumitomo Pharma suffered two late-stage defeats in another psychiatric indication. In July 2023, the companies announced that its investigational TAAR1 agonist ulotaront failed the Phase III studies DIAMOND 1 and DIAMOND 2 in schizophrenia patients with acute psychosis. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com .

Phase 3Clinical Result

30 Oct 2023

·www.biospace.com

Otsuka’s Centanafadine Shows Promise in Phase III Pediatric ADHD Studies

Pictured: Girl student having trouble concentrating/iStock, PeopleImages Otsuka Pharmaceutical on Friday posted top-line data from two Phase III studies, demonstrating that its attention deficit/hyperactivity disorder candidate centanafadine significantly improves symptoms in children and teenagers. Friday’s readouts come from attention deficit/hyperactivity disorder (ADHD) trials that are largely similar in design, employing three arms and fixed high or low doses of centanafadine which were given compared to placebo on a double-blinded basis. The main difference is in the study populations: one enrolled adolescent participants between the ages of 13 and 17 years, while the other included children aged six to 12 years. In the adolescent study, patients treated with high-dose centanafadine saw significantly better scores on the ADHD Rating Scale version 5 (ADHD-RS-5), a validated tool used to assess the severity of ADHD and the study’s primary endpoint. The average effect of both the high and low centanafadine doses was also significantly better than placebo. Centanafadine was similarly effective in children. ADHD-RS-5 scores significantly improved in patients who were treated with high-dose centanafadine, and the average treatment effect in both high-dose and low-dose groups was likewise statistically better than placebo. In the adolescent and pediatric trials, the benefits of high-dose centanafadine became apparent as early as the first post-baseline timepoint at week one, which was sustained for the rest of the study periods. However, both low-dose arms did not see significantly improved ADHD-RS-5 scores versus placebo. In terms of safety, pooling data from both studies demonstrated a tolerability pro was consistent with centanafadine’s broader clinical development program. The most common side effects included nausea, upper abdominal pain, somnolence and fatigue. While the full results from both studies are not yet available, these data “demonstrate centanafadine has the potential to offer a new treatment option for children and adolescents who live with ADHD,” John Kraus, chief medical officer of U.S. subsidiary Otsuka Pharmaceutical Development and Commercialization, said in a statement. Otsuka will submit complete data and analyses from both trials for scientific publication. The company will also use these findings, along with clinical pharmacology studies and long-term stability data, to build a New Drug Application for centanafadine in this indication. Friday’s ADHD readout comes months after Otsuka and partner Sumitomo Pharma suffered two late-stage defeats in another psychiatric indication. In July 2023, the companies announced that its investigational TAAR1 agonist ulotaront failed the Phase III studies DIAMOND 1 and DIAMOND 2 in schizophrenia patients with acute psychosis. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Phase 3Clinical Result

100 Deals associated with Centanafadine Hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
D10698	Centanafadine Hydrochloride	-	DB14841

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Generalized anxiety disorder	Phase 3	United States	Otsuka Pharmaceutical Development & Commercialization, Inc.	26 Mar 2025
Attention Deficit Disorder With Hyperactivity	Phase 3	United States	Otsuka Pharmaceutical Development & Commercialization, Inc.	02 Feb 2022
Attention Deficit Disorder	Phase 3	United States	Otsuka Pharmaceutical Development & Commercialization, Inc.	16 Jan 2019
Depressive Disorder, Major	Phase 2	United States	Otsuka Pharmaceutical Development & Commercialization, Inc.	12 Sep 2022
Binge-Eating Disorder	Phase 2	United States	Otsuka Pharmaceutical Development & Commercialization, Inc.	16 Dec 2021
Smoking Cessation	Phase 2	United States	Otsuka Pharmaceutical Development & Commercialization, Inc.	15 Sep 2021

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05257265 (A Trial of Centanafadine Efficacy and Safety in Adolescents With Attention-Deficit/Hyperactivity Disorder, Pubmed \| J Am Acad Child Adolesc Psychiatry)	Phase 3	Attention Deficit Disorder With Hyperactivity	459	Centanafadine 164.4 mg	bmxtuyfcbd(qusutkpeue) = 1 event in 164.4 mg group rtemxvlooa (qocpzypwws ) View more	Positive	01 Jul 2025
				Centanafadine 328.8 mg
NCT05066724 (CTgov)	Phase 2	Smoking Cessation	50	Centanafadine	dlsrbrvzes = zqxjjtjuqd qqhwcregoh (mrccxrkpkk, odxhonpcpj - boyefbxeev) View more	-	13 Jun 2025
NCT03605849 (CTgov)	Phase 3	Attention Deficit Disorder	662	Centanafadine SR (Prior Centanafadine SR 200 mg)	ehhvqeuefu = sbevbepbfu mlpxjixgat (ptbtzjhwsa, adywbmtxtp - kxncfltxrf) View more	-	01 Oct 2024
				Centanafadine SR (Prior Centanafadine SR 400 mg)	ehhvqeuefu = tlbxfomoxg mlpxjixgat (ptbtzjhwsa, mmrcjogylc - dgnihldvrk) View more
NCT03605836 \| NCT00334880 \| NCT00190736 \| NCT04016779 (Pubmed)	Not Applicable	Attention Deficit Disorder With Hyperactivity	-	Centanafadine sustained-release	gtryhkpnfo(bgzyshdxaz) = 6.58-point difference goolehdxub (oeerbfzoid )	Positive	01 Jun 2024
NCT05257265 (NEWS) Manual	Phase 3	Attention Deficit Disorder With Hyperactivity	-	Centanafadine (high dose)	tgvsjupetf(uxjgsfblha) = In a pooled analysis across the two studies, the most frequently observed side effects for centanafadine (>2 percent and more frequent than placebo) included decreased appetite, nausea, rash, fatigue, upper abdominal pain and somnolence.Overall, the safety and tolerability results were consistent with the profile of centanafadine seen within the wider clinical development program. jjsfhpeooz (xxdeiffkyw )	Positive	27 Oct 2023
				Centanafadine (low dose)
NCT05428033 (NEWS) Manual	Phase 3	Attention Deficit Disorder With Hyperactivity	-	Centanafadine (high dose)	dotyosymtd(vnmcwovdnq) = In a pooled analysis across the two studies, the most frequently observed side effects for centanafadine (>2 percent and more frequent than placebo) included decreased appetite, nausea, rash, fatigue, upper abdominal pain and somnolence.Overall, the safety and tolerability results were consistent with the profile of centanafadine seen within the wider clinical development program. qnphvbwelz (ofpqapgvqa )	Positive	27 Oct 2023
				Centanafadine (low dose)
NCT04081363 (CTgov)	Phase 2	Attention Deficit Disorder With Hyperactivity	13	Centanafadine (Swallowed Capsules Cohort)	nryjtrbffz(plqsbagugc) = lbodwaerio iuofinqqod (uoraapemdm, 51.4) View more	-	13 Jan 2023
				Centanafadine (Sprinkled Onto Applesauce Cohort)	nryjtrbffz(plqsbagugc) = dbimdhzgrv iuofinqqod (uoraapemdm, 52.8) View more
NCT01939353 (CTgov)	Phase 2	Attention Deficit Disorder With Hyperactivity	45	Placebo+CTN SR	jpvpxqeohk(hyqorugloj) = ksbrgbcgza uuhjrnkoyv (rvsxghicec, 6.19) View more	-	18 Oct 2021
NCT03605836 (CTgov)	Phase 3	Attention Deficit Disorder	590	Centanafadine SR (Double-blind Treatment Period: Centanafadine SR 200 mg)	ektpbhlion(pplbukbykh) = iuqzpiaasg fmpduulhku (htvvjuyooo, 0.96) View more	-	18 Oct 2021
				Centanafadine SR (Double-blind Treatment Period: Centanafadine SR 400 mg)	ektpbhlion(pplbukbykh) = ouxhlzbjdy fmpduulhku (htvvjuyooo, 0.99) View more
NCT03605680 (CTgov)	Phase 3	Attention Deficit Disorder	604	Centanafadine SR (Double-blind Treatment Period: Centanafadine SR 200 mg)	wivaqxzdyc(hkjqvzyivo) = gtjopclvdq qfziqyygqi (qnyesjnmpn, 0.99) View more	-	05 May 2021
				Centanafadine SR (Double-blind Treatment Period: Centanafadine SR 400 mg)	wivaqxzdyc(hkjqvzyivo) = avzjqurpug qfziqyygqi (qnyesjnmpn, 0.98) View more