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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: CTN 1 × 328.8 mg capsule, Then CTN 2 × 164.4 mg capsules | Experimental | 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. |
|
| Cohort 1: CTN 2 × 164.4 mg capsule, Then CTN 1 × 328.8 mg capsules | Experimental | 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. |
|
| Cohort 2: CTN Fasted State, Then CTN Fed state | Experimental | 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. |
|
| Cohort 2: CTN Fed state, Then CTN Fasted state | Experimental | 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. |
|
| Cohort 3: CTN 200 mg SR, Then CTN164.4 mg XR, Then CTN 400 mg SR, Then CTN 328.8 mg XR | Experimental | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CTN XR (TBM) | Drug | Oral capsules |
|
| Measure | Description | 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 |
| Measure | Description | 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 |
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Inclusion Criteria:
Body mass index (BMI) between 19.0 to 32.0 kilograms per square meter (kg/m^2) (inclusive).
In good health as determined by:
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:
Note: Other protocol-specified Inclusion/Exclusion criteria may apply.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| ICON Lenexa | Lenexa | Kansas | 66219 | United States | ||
| ICON Salt Lake City |
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.
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.
Otsuka will share data on the Vivli data sharing platform: https://vivli.org/ourmember/Otsuka/
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|
| Cohort 3: CTN 164.4 mg XR, Then CTN 200 mg SR, Then CTN 328.8 mg XR, Then CTN 400 mg SR | Experimental | 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. |
|
| Cohort 3: CTN 400 mg SR, Then CTN 328.8 mg XR, Then CTN 200 mg SR, Then CTN 164.4 mg XR | Experimental | 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. |
|
| Cohort 3: CTN 328.8 mg XR, Then CTN 400 mg SR, Then CTN 164.4 mg XR, Then CTN 200 mg SR | Experimental | 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. |
|
| Cohort 4: CTN 164.4mg (Clin), Then CTN 164.4mg (TBM), Then CTN 328.8mg (Clin) Then CTN 328.8mg (TBM) | Experimental | 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. |
|
| Cohort 4: CTN 164.4mg (TBM), Then CTN 164.4mg (Clin), Then CTN 328.8mg (TBM) Then CTN 328.8mg (Clin) | Experimental | 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. |
|
| Cohort 4: CTN 328.8mg (Clin), Then CTN 328.8mg (TBM), Then CTN 164.4mg (Clin),Then CTN 164.4mg (TBM) | Experimental | 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. |
|
| Cohort 4: CTN 328.8mg (TBM), Then CTN 328.8mg (Clin), Then CTN 164.4mg (TBM) Then CTN 164.4mg (Clin) | Experimental | 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. |
|
| Cohort 5: CTN 328.8 mg XR (TBM), Then CTN 400 mg SR | Experimental | 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. |
|
| Cohort 5: CTN 400 mg SR, Then CTN 328.8 mg XR (TBM) | Experimental | 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. |
|
|
| CTN SR | Drug | Oral tablets |
|
|
| CTN XR (Clin) | Drug | Oral capsules |
|
|
| 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 |
| Millcreek |
| Utah |
| 84124 |
| United States |
| ID | Term |
|---|---|
| D001289 | Attention Deficit Disorder with Hyperactivity |
| ID | Term |
|---|---|
| D019958 | Attention Deficit and Disruptive Behavior Disorders |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C574080 | 1-(naphthalen-2-yl)-3-azabicyclo(3.1.0)hexane |
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