A Phase 1, Randomized, Single-Dose, 3-Way, Crossover Study to Compare the Relative Bioavailability, Pharmacokinetics, Safety and Tolerability of AVP-923 (Dextromethorphan Hydrobromide and Quinidine Sulfate Capsules) Administered in Applesauce or Via a Nasogastric Feeding Tube With Administration of a Capsule in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Mean time to maximum plasma concentration (Tmax) for the analytes DM, DX, 3-MM, and Q
研究概览
简要总结
This study will be conducted to evaluate the relative bioavailability, pharmacokinetics, safety, and tolerability of AVP-923 (dextromethorphan hydrobromide [DM] and quinidine sulfate [Q] capsules) when the contents of a capsule are administered in applesauce or via a nasogastric feeding tube, compared with administration of a capsule in healthy, fasting, adult participants.
详细描述
This is an open-label, single-center, randomized, single-dose, 3-treatment, 3-period, 6-sequence crossover study in healthy adult participants consisting of approximately 7 weeks of treatment. The study population will be limited to extensive metabolizers of cytochrome P450 (CYP) 2D6.
Approximately 18 participants will be randomly assigned to 1 of 6 sequences (ABC, ACB, BAC, BCA, CAB, CBA).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy adults, 18 to 65 years of age, inclusive
- •Willing to sign informed consent form
- •Cytochrome P450 2D6 genotype that confers extensive metabolizer profile (as per documented phenotype interpretation from local laboratory and approval from Avanir)
排除标准
- •History or presence of significant pulmonary, hepatic, renal, hematologic, allergic, endocrine (including diabetes), immunologic, dermatologic, neurologic (including history or presence of seizures or convulsive disorders), psychiatric disease (including history of suicidal ideation or behavior) or any eating disorder deemed clinically significant by the investigator
- •History or presence of significant cardiovascular disease, including complete heart block, QT interval corrected for heart rate (QTc) prolongation, and/or torsades de pointes
- •History or presence of any gastrointestinal (GI) disease or condition that could compromise participant safety or affect the absorption of study drug, including GI ulcers, GI bleeding, esophageal or gastric varices, and dyspepsia requiring regular (i.e., more frequently than once a month) use of acid-reducing drugs
- •Known hypersensitivity/intolerance to dextromethorphan or quinidine
- •Participants whom the principal investigator or his delegate deems to be ineligible
研究组 & 干预措施
AVP-923-20/10 capsule
Participants will receive a single AVP-923-20/10 (dextromethorphan hydrobromide [DM] 20 milligram [mg]/quinidine sulfate [Q] 10 mg) capsule administered orally.
干预措施: AVP-923 (Drug)
AVP-923-20/10 via applesauce
Participants will receive the contents from a single AVP-923-20/10 capsule mixed and consumed in 1 tablespoon of applesauce.
干预措施: AVP-923 (Drug)
AVP-923-20/10 via nasogastric feeding tube
Participants will receive the contents from a single AVP-923-20/10 capsule solubilized in feeding solution and administered through a nasogastric feeding tube.
干预措施: AVP-923 (Drug)
结局指标
主要结局
Mean time to maximum plasma concentration (Tmax) for the analytes DM, DX, 3-MM, and Q
时间窗: pre-dose (within 30 minutes prior to dosing) and post-dose (up to 48 hours after drug administration)
Mean area under the concentration time curve (AUC) from time 0 to time of last measurable concentration (AUC0-t) for the analytes dextromethorphan (DM), dextrorphan (DX), 3-methoxymorphinan (3-MM), and quinidine (Q)
时间窗: pre-dose (within 30 minutes prior to dosing) and post-dose (up to 48 hours after drug administration)
Mean AUC from time 0 to infinity (AUC0-inf) for the analytes DM, DX, 3-MM, and Q
时间窗: pre-dose (within 30 minutes prior to dosing) and post-dose (up to 48 hours after drug administration)
Mean maximum plasma concentration (Cmax) for the analytes DM, DX, 3-MM, and Q
时间窗: pre-dose (within 30 minutes prior to dosing) and post-dose (up to 48 hours after drug administration)
Mean apparent terminal elimination half-life (t1/2) for the analytes DM, DX, 3-MM, and Q
时间窗: pre-dose (within 30 minutes prior to dosing) and post-dose (up to 48 hours after drug administration)
Mean apparent elimination rate constant (kel) for the analytes DM, DX, 3-MM, and Q
时间窗: pre-dose (within 30 minutes prior to dosing) and post-dose (up to 48 hours after drug administration)
次要结局
- Number of participants with any clinically significant electrocardiogram evaluation(3 weeks)
- Number of participants with any clinically significant physical examination evaluation(3 weeks)
- Number of participants with any adverse event(3 weeks)
- Number of participants with any clinically significant clinical laboratory evaluation(3 weeks)
- Number of participants with any clinically significant vital sign value(3 weeks)
- Number of participants with the indicated score on the Columbia-Suicide Severity Rating Scale (C-SSRS)(3 weeks)