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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 174
- 试验地点
- 2
- 主要终点
- Cohorts 1, 2, 3, and 4: Maximum Plasma Concentration (Cmax) of CTN
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Body mass index (BMI) between 19.0 to 32.0 kilograms per square meter (kg/m^2) (inclusive).
- •In good health as determined by:
- •Medical history
- •Physical examination
- •Electrocardiogram (ECG)
- •Serum/urine chemistry, hematology, and serology tests.
- •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.
排除标准
- •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.
- •History of drug and/or alcohol abuse within 2 years prior to screening.
- •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.
- •History of any significant drug allergy or known or suspected hypersensitivity.
- •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.
- •Any participant who, in the opinion of the investigator, should not participate in the trial.
- •Note: Other protocol-specified Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
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.
干预措施: CTN SR (Drug)
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.
干预措施: CTN XR (TBM) (Drug)
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.
干预措施: CTN XR (TBM) (Drug)
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.
干预措施: CTN XR (TBM) (Drug)
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.
干预措施: CTN XR (TBM) (Drug)
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.
干预措施: CTN XR (TBM) (Drug)
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.
干预措施: CTN SR (Drug)
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.
干预措施: CTN XR (TBM) (Drug)
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.
干预措施: CTN SR (Drug)
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.
干预措施: CTN XR (TBM) (Drug)
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.
干预措施: CTN SR (Drug)
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.
干预措施: CTN XR (TBM) (Drug)
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.
干预措施: CTN SR (Drug)
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.
干预措施: CTN XR (TBM) (Drug)
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.
干预措施: CTN XR (Clin) (Drug)
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.
干预措施: CTN XR (TBM) (Drug)
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.
干预措施: CTN XR (Clin) (Drug)
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.
干预措施: CTN XR (TBM) (Drug)
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.
干预措施: CTN XR (Clin) (Drug)
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.
干预措施: CTN XR (TBM) (Drug)
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.
干预措施: CTN XR (Clin) (Drug)
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.
干预措施: CTN XR (TBM) (Drug)
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.
干预措施: CTN XR (TBM) (Drug)
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.
干预措施: CTN SR (Drug)
结局指标
主要结局
Cohorts 1, 2, 3, and 4: Maximum Plasma Concentration (Cmax) of CTN
时间窗: 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
时间窗: 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
时间窗: Cohorts 1 and 2: Up to Day 6; Cohorts 3 and 4: Up to Day 12
Cohort 5: Cmax of CTN
时间窗: Up to Day 11
Cohort 5: Area Under the Plasma Concentration-time Curve During the Dosing Interval at Steady-state of CTN XR
时间窗: 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
时间窗: 24 Hours postdose up to Day 10
Cohort 5: Minimum Plasma Concentration During a Dosing Interval (Cmin) of CTN
时间窗: Up to Day 11
次要结局
- 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)
- 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)
- 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)
- 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)