A Trial to Characterize Differences in Blood Levels of Different Lots of Centanafadine QD XR and to Understand the Effect of Food on Blood Levels

A Multiple-arm, Phase 1, Open-label Trial to Determine Dose Strength Equivalence and Effect of Food on To-Be-Marketed Centanafadine QD XR Capsules, Bioequivalence Between Clinical and To-Be-Marketed QD XR Capsules and Relative Bioavailability of To-Be-Marketed QD XR Capsules to SR Tablets in Healthy Adults

The purpose of this study is to evaluate the dose strength equivalence of to-be-marketed (TBM) centanafadine (CTN) once daily (QD) extended release (XR) when administered as 2 capsules of 164.4 milligrams (mg) or as a single capsule of 328.8 mg, effect of food on the absorption of the TBM CTN QD XR capsule, and relative bioavailability of clinical (Clin) CTN sustained release (SR) tablets to the TBM CTN QD XR capsules.

Study Overview

• Status: Completed
• Conditions: Attention Deficit Disorder With Hyperactivity
• Intervention / Treatment: Drug: CTN XR (TBM); Drug: CTN SR; Drug: CTN XR (Clin)

• Study Type: Interventional
• Enrollment (Actual): 174
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • ICON Lenexa
  • Utah
    • Millcreek, Utah, United States, 84124
      • ICON Salt Lake City

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Body mass index (BMI) between 19.0 to 32.0 kilograms per square meter (kg/m^2) (inclusive).

2. In good health as determined by:

   • Medical history
   • Physical examination
   • Electrocardiogram (ECG)
   • Serum/urine chemistry, hematology, and serology tests.
3. Ability to provide written, informed consent prior to initiation of any trial-related procedures, and ability, in the opinion of the investigator, to comply with all the requirements of the trial.

Exclusion Criteria:

1. Clinically significant abnormality in past medical history, or at the screening physical examination, that in the investigator's or sponsor's opinion may place the participant at risk or interfere with outcome variables including absorption, distribution, metabolism, and excretion of drug. This includes, but is not limited to, history of or concurrent cardiac, hepatic, renal, neurologic, endocrine, gastrointestinal, respiratory, hematologic, and immunologic disease or cholecystectomy.
2. History of drug and/or alcohol abuse within 2 years prior to screening.
3. History of or current hepatitis or AIDS or carriers of hepatitis B surface antigen (HBsAg) and/or hepatitis C antibodies (anti-HCV), or HIV antibodies.
4. History of any significant drug allergy or known or suspected hypersensitivity.
5. A positive urine or breath alcohol test and/or urine drug screen for substance of abuse at screening or upon admission to the trial site.
6. Any participant who, in the opinion of the investigator, should not participate in the trial.

Note: Other protocol-specified Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

14

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: CTN 1 × 328.8 mg capsule, Then CTN 2 × 164.4 mg capsules; Participants first receive a 1 × 328.8 mg CTN capsule, orally, on Day 1. Then, they receive 2 × 164.4 mg CTN capsules, orally, on Day 4.	Drug: CTN XR (TBM); Oral capsules; Other Names: EB-1020
Experimental: Cohort 1: CTN 2 × 164.4 mg capsule, Then CTN 1 × 328.8 mg capsules; Participants first receive 2 × 164.4 mg CTN capsules, orally, on Day 1. Then, they receive 1 × 328.8 mg CTN capsule, orally, on Day 4.	Drug: CTN XR (TBM); Oral capsules; Other Names: EB-1020
Experimental: Cohort 2: CTN Fasted State, Then CTN Fed state; Participants first receive 1 × 328.8 mg CTN capsules, orally, in the fasted state, on Day 1. Then, they receive 1 × 328.8 mg CTN capsule, orally, in the fed state, on Day 4.	Drug: CTN XR (TBM); Oral capsules; Other Names: EB-1020
Experimental: Cohort 2: CTN Fed state, Then CTN Fasted state; Participants first receive 1 × 328.8 mg CTN capsules, orally, in the fed state, on Day 1. Then, they receive 1 × 328.8 mg CTN capsule, orally, in the fasted state, on Day 4.	Drug: CTN XR (TBM); Oral capsules; Other Names: EB-1020
Experimental: Cohort 3: CTN 200 mg SR, Then CTN164.4 mg XR, Then CTN 400 mg SR, Then CTN 328.8 mg XR; Participants first receive CTN 200 mg SR, tablets, orally on Day 1 followed by CTN 164.4 mg XR, capsules, orally on Day 4. Participants then receive CTN 400 mg SR, tablets, orally on Day 7, followed by CTN 328.8 mg XR, capsules, orally on Day 10.	Drug: CTN XR (TBM); Oral capsules; Other Names: EB-1020; Drug: CTN SR; Oral tablets; Other Names: EB-1020
Experimental: Cohort 3: CTN 164.4 mg XR, Then CTN 200 mg SR, Then CTN 328.8 mg XR, Then CTN 400 mg SR; Participants first receive CTN 164.4 mg XR, capsules, orally on Day 1 followed by CTN 200 mg SR, tablets, orally on Day 4. Participants then receive CTN 328.8 mg XR, capsules, orally on Day 7, followed by CTN 400 mg SR, tablets, orally on Day 10.	Drug: CTN XR (TBM); Oral capsules; Other Names: EB-1020; Drug: CTN SR; Oral tablets; Other Names: EB-1020
Experimental: Cohort 3: CTN 400 mg SR, Then CTN 328.8 mg XR, Then CTN 200 mg SR, Then CTN 164.4 mg XR; Participants first receive CTN 400 mg SR, tablets, orally on Day 1 followed by CTN 328.8 mg XR, capsules, orally on Day 4. Participants then receive CTN 200 mg SR, tablets, orally on Day 7, followed by CTN 164.4 mg XR, capsules, orally on Day 10.	Drug: CTN XR (TBM); Oral capsules; Other Names: EB-1020; Drug: CTN SR; Oral tablets; Other Names: EB-1020
Experimental: Cohort 3: CTN 328.8 mg XR, Then CTN 400 mg SR, Then CTN 164.4 mg XR, Then CTN 200 mg SR; Participants first receive CTN 328.8 mg XR, capsules, orally on Day 1 followed by CTN 400 mg SR, tablets, orally on Day 4. Participants then receive CTN 164.4 mg XR, capsules, orally on Day 7, followed by CTN 200 mg SR, tablets, orally on Day 10.	Drug: CTN XR (TBM); Oral capsules; Other Names: EB-1020; Drug: CTN SR; Oral tablets; Other Names: EB-1020
Experimental: Cohort 4: CTN 164.4mg (Clin), Then CTN 164.4mg (TBM), Then CTN 328.8mg (Clin) Then CTN 328.8mg (TBM); Participants first receive CTN 164.4 mg XR (Clin), capsules, orally on Day 1 followed by CTN 164.4 mg XR (TBM), capsules, orally on Day 4. Participants then receive CTN 328.8 mg XR (Clin), capsules, orally on Day 7, followed by CTN 328.8 mg XR (TBM), capsules, orally on Day 10.	Drug: CTN XR (TBM); Oral capsules; Other Names: EB-1020; Drug: CTN XR (Clin); Oral capsules; Other Names: EB-1020
Experimental: Cohort 4: CTN 164.4mg (TBM), Then CTN 164.4mg (Clin), Then CTN 328.8mg (TBM) Then CTN 328.8mg (Clin); Participants first receive CTN 164.4 mg XR (TBM), capsules, orally on Day 1 followed by CTN 164.4 mg XR (Clin), capsules, orally on Day 4. Participants then receive CTN 328.8 mg XR (TBM), capsules, orally on Day 7, followed by CTN 328.8 mg XR (Clin), capsules, orally on Day 10.	Drug: CTN XR (TBM); Oral capsules; Other Names: EB-1020; Drug: CTN XR (Clin); Oral capsules; Other Names: EB-1020
Experimental: Cohort 4: CTN 328.8mg (Clin), Then CTN 328.8mg (TBM), Then CTN 164.4mg (Clin),Then CTN 164.4mg (TBM); Participants first receive CTN 328.8 mg XR (Clin), capsules, orally on Day 1 followed by CTN 328.8 mg XR (TBM), capsules, orally on Day 4. Participants then receive CTN 164.4 mg XR (Clin), capsules, orally on Day 7, followed by CTN 164.4 mg XR (TBM), capsules, orally on Day 10.	Drug: CTN XR (TBM); Oral capsules; Other Names: EB-1020; Drug: CTN XR (Clin); Oral capsules; Other Names: EB-1020
Experimental: Cohort 4: CTN 328.8mg (TBM), Then CTN 328.8mg (Clin), Then CTN 164.4mg (TBM) Then CTN 164.4mg (Clin); Participants first receive CTN 328.8 mg XR (TBM), capsules, orally on Day 1 followed by CTN 328.8 mg XR (Clin), capsules, orally on Day 4. Participants then receive CTN 164.4 mg XR (TBM), capsules, orally on Day 7, followed by CTN 164.4 mg XR (Clin), capsules, orally on Day 10.	Drug: CTN XR (TBM); Oral capsules; Other Names: EB-1020; Drug: CTN XR (Clin); Oral capsules; Other Names: EB-1020
Experimental: Cohort 5: CTN 328.8 mg XR (TBM), Then CTN 400 mg SR; Participants first receive CTN 328.8 mg XR (TBM), capsules, orally, once a day (QD) from Day 1 to Day 5. Then, they receive CTN 400 mg SR, tablets, orally, from Day 6 to Day 10.	Drug: CTN XR (TBM); Oral capsules; Other Names: EB-1020; Drug: CTN SR; Oral tablets; Other Names: EB-1020
Experimental: Cohort 5: CTN 400 mg SR, Then CTN 328.8 mg XR (TBM); Participants first receive CTN 400 mg SR, tablets, orally from Day 1 to Day 5. Then, they will receive CTN 328.8 mg XR (TBM), capsules, orally, QD from Day 6 to Day 10.	Drug: CTN XR (TBM); Oral capsules; Other Names: EB-1020; Drug: CTN SR; Oral tablets; Other Names: EB-1020

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cohorts 1, 2, 3, and 4: Maximum Plasma Concentration (Cmax) of CTN	Cohorts 1 and 2: Up to Day 6; Cohorts 3 and 4: Up to Day 12
Cohorts 1, 2, 3, and 4: Area Under the Plasma Concentration-time Curve Calculated From Time 0 to Time t (AUCt) of CTN	Cohorts 1 and 2: Up to Day 6; Cohorts 3 and 4: Up to Day 12
Cohorts 1, 2, 3, and 4: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity of CTN	Cohorts 1 and 2: Up to Day 6; Cohorts 3 and 4: Up to Day 12
Cohort 5: Cmax of CTN	Up to Day 11
Cohort 5: Area Under the Plasma Concentration-time Curve During the Dosing Interval at Steady-state of CTN XR	Up to Day 11
Cohort 5: Area Under the Drug Concentration-time Curve From Time Zero Predose to 24 hours Postdose (AUC0-24h) of CTN SR	24 Hours postdose up to Day 10
Cohort 5: Minimum Plasma Concentration During a Dosing Interval (Cmin) of CTN	Up to Day 11

Secondary Outcome Measures

Outcome Measure	Time Frame
Cohorts 1, 2, 3, and 4: Percentage (%) Extrapolated AUC of CTN and its Metabolites	Cohorts 1 and 2: Up to Day 6; Cohorts 3 and 4: Up to Day 12
Cohorts 1, 2, 3, and 4: AUC0-24h of CTN and its Metabolites	Cohorts 1 and 2: 24 Hours Postdose up to Day 4; Cohorts 3 and 4: 24 Hours Postdose up to Day 10
Cohort 1, 2, 3, and 4: Time to Maximum (peak) Plasma Concentration (tmax) of CTN and its Metabolites	Cohorts 1 and 2: Up to Day 6; Cohorts 3 and 4: Up to Day 12
Cohort 1, 2, 3, and 4: Apparent Clearance (CL/F) of CTN and its Metabolites	Cohorts 1 and 2: Up to Day 6; Cohorts 3 and 4: Up to Day 12
Cohort 1, 2, 3, and 4: Volume of Distribution (Vz/F) of CTN	Cohorts 1 and 2: Up to Day 6; Cohorts 3 and 4: Up to Day 12
Cohort 1, 2, 3, and 4: Terminal Phase Elimination Half-Life (t1/2,z) of CTN and its Metabolites	Cohorts 1 and 2: Up to Day 6; Cohorts 3 and 4: Up to Day 12
Cohort 5: Tmax of CTN and its Metabolites	Up to Day 11
Cohort 5: CL/F of CTN	Up to Day 11
All Cohorts: Number of Participants With Adverse Events (AEs)	Cohorts 1 and 2: Up to Day 11; Cohorts 3, 4, and 5: Up to Day 17
All Cohorts: Number of Participants With Potentially Clinically Relevant Laboratory Tests	Cohorts 1 and 2: Up to Day 6; Cohorts 3 and 4: Up to Day 12; Cohort 5: Up to Day 11
All Cohorts: Number of Participants With Potentially Clinically Relevant Vital Signs	Cohorts 1 and 2: Up to Day 6; Cohorts 3 and 4: Up to Day 12; Cohort 5: Up to Day 11
All Cohorts: Number of Participants With Potentially Clinically Relevant 12-Lead Electrocardiogram (ECG) Tests	Cohorts 1 and 2: Up to Day 6; Cohorts 3 and 4: Up to Day 12; Cohort 5: Up to Day 11
All Cohorts: Percentage of Participants With Suicidal Ideation or Suicidal Behavior Using the Columbia-Suicide Severity Rating Scale (C-SSRS)	Cohorts 1 and 2: Up to Day 6; Cohorts 3 and 4: Up to Day 12; Cohort 5: Up to Day 11

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 29, 2024
• Primary Completion (Actual): December 30, 2024
• Study Completion (Actual): December 30, 2024

Study Registration Dates

• First Submitted: November 19, 2025
• First Submitted That Met QC Criteria: November 19, 2025
• First Posted (Estimated): November 28, 2025

Study Record Updates

• Last Update Posted (Actual): December 11, 2025
• Last Update Submitted That Met QC Criteria: December 4, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Healthy Volunteers
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Attention Deficit and Disruptive Behavior Disorders; Attention Deficit Disorder with Hyperactivity; 1-(naphthalen-2-yl)-3-azabicyclo(3.1.0)hexane
• Other Study ID Numbers: 405-201-00157

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
• IPD Sharing Time Frame: Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.
• IPD Sharing Access Criteria: Otsuka will share data on the Vivli data sharing platform: https://vivli.org/ourmember/Otsuka/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes