An Open-Label, Randomized, Crossover Study to Evaluate Bioavailability of a Single 12 mg Dose of Perampanel for Three Intravenous Infusion Durations Relative to a Single 12 mg Perampanel Oral Tablet in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Eisai Inc.
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Mean maximum observed concentration (Cmax) postdose of perampanel
研究概览
简要总结
This study will be conducted to evaluate the bioavailability of a single 12 milligram (mg) dose of perampanel intravenous infusions of different durations relative to a single 12 mg dose of perampanel oral tablet in healthy participants.
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
- 20 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Non-smoking, male or female, between 20 and 55 years of age (inclusive) at the time of informed consent
- •Body mass index (BMI) of 18 to 32 kilograms per meters squared (kg/m^2) (inclusive) at Screening
- •For Japanese participants:
- •i. Born in Japan to Japanese parents and grandparents of Japanese descent; ii. Have been living outside Japan for less than 5 years; and iii. Lifestyle, including diet, has not changed significantly since leaving Japan
- •Provide written informed consent
- •Willing and able to comply with all aspects of the protocol
排除标准
- •Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks of dosing
- •Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin [ß-hCG]). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
- •Females of childbearing potential who:
- •i. Within 28 days before study entry, did not use a highly effective method of contraception, which includes any of the following:
- •total abstinence (if it is their preferred and usual lifestyle);
- •an intrauterine device or intrauterine hormone-releasing system (IUS);
- •a contraceptive implant;
- •an oral contraceptive (with additional barrier method). Participant must be on a stable dose of the same oral contraceptive product for at least 28 days before dosing and throughout the study and for 28 days after study drug discontinuation; or
- •have a vasectomized partner with confirmed azoospermia ii. Do not agree to use a highly effective method of contraception (as described above) throughout the entire study period and for 28 days after study drug discontinuation NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).
- •Evidence of disease that may influence the outcome of the study within 4 weeks of dosing, eg, psychiatric disorders and disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, cardiovascular system, or participants who have a congenital abnormality in metabolism
- •Any history of gastrointestinal surgery that may affect pharmacokinetics (PK) profiles of perampanel, eg, hepatectomy, nephrectomy, digestive organ resection or any gastrointestinal procedure for the purpose of weight loss (including Lapband™), which would slow gastric emptying
- •Any clinically abnormal symptom or organ impairment found by medical history at Screening, and physical examinations, vital signs, electrocardiogram (ECG) finding, or laboratory test results that require medical treatment at Screening or Baseline. A single repeat test for an abnormal vital sign and/or laboratory value is permitted, at the discretion of the Investigator.
- •A prolonged QT/QTc interval (QTc >450 milliseconds [msec]) as demonstrated upon repeat ECG at Screening or Baseline
- •Heart rate <50 or >100 beats per minute at Screening or Baseline
- •History of ischemic heart disease (eg, acute coronary syndromes, stable angina), syncope or cardiac arrhythmias
- •Systolic blood pressure >140 millimeters of mercury (mmHg) or <90 mmHg or diastolic blood pressure >90 mmHg or <60 mmHg at Screening or Baseline
- •Hemoglobin <12.5 grams per deciliter (g/dL) or hematocrit ≤38% for males and postmenopausal females and hemoglobin <10 g/dL or hematocrit ≤33% for pre-menopausal females at Screening
- •Participants who experienced a weight loss or gain of >10% between Screening and the first clinic check-in (Day -1)
- •Participants who received blood products within 4 weeks, donated blood within 8 weeks, or donated plasma within 1 week of dosing
- •Hypersensitivity to the study drug or any of its excipients
- •Known severe or clinically significant history of food allergies or presently experiencing significant seasonal or perennial allergy at Screening
- •Known to be human immunodeficiency virus (HIV) positive at Screening
- •Active viral hepatitis (B or C) as demonstrated by positive serology at Screening
- •History of drug or alcohol dependency or abuse within approximately the last 2 years or who have a positive urine drug, cotinine, or alcohol test at Screening or Baseline
- •Engagement in strenuous exercise within 2 weeks before dosing (eg, marathon runners, weight lifters)
- •Currently enrolled in another clinical trial or used any investigational drug or device within 30 days preceding informed consent
- •Restrictions on prior and concomitant medications, food and beverages:
- •i. Prescription drugs are prohibited within 4 weeks of dosing and over-the-counter (OTC) drugs within 2 weeks before dosing or throughout the Treatment Phase ii. Smoking or use of tobacco or nicotine-containing products is prohibited within 4 weeks before dosing and throughout the Treatment Phase iii. Intake of caffeinated beverages or food is prohibited within 72 hours before dosing and until 72 hours postdose iv. Intake of nutritional supplements, juice, and herbal preparations or other foods or beverages that may affect Cytochrome P450 (CYP) 3A4 enzyme or transporters (eg, alcohol, grapefruit, grapefruit juice, grapefruit-containing beverages, apple or orange juice, vegetables from the mustard green family [eg, kale, broccoli, watercress, collard greens, kohlrabi, brussels sprouts, mustard] and charbroiled meats) is prohibited within 2 weeks before dosing and throughout the Treatment Phase v. Intake of herbal preparations containing St. John's Wort is prohibited within 4 weeks before dosing and throughout the Treatment Phase
研究组 & 干预措施
Perampanel: 30-minute IV infusion and 12 mg oral tablet
Participants will be randomized on Day 1 of Treatment Period 1 to receive either a single 12 milligram (mg) dose of perampanel intravenous (IV) infusion (30-minute duration) or a single 12 mg oral tablet after an overnight fast. Participants will then receive the alternative treatment on Day 43 of Treatment Period 2. Drug administration will be separated by a washout of at least 6 weeks between the 2 treatment periods.
干预措施: Perampanel (Drug)
Perampanel: 60-minute IV infusion and 12 mg oral tablet
Participants will be randomized on Day 1 of Treatment Period 1 to receive either a single 12 mg dose of perampanel IV infusion (60-minute duration) or a single 12 mg oral tablet after an overnight fast. Participants will then receive the alternative treatment on Day 43 of Treatment Period 2. Drug administration will be separated by a washout of at least 6 weeks between the 2 treatment periods.
干预措施: Perampanel (Drug)
Perampanel: 90-minute IV infusion and 12 mg oral tablet
Participants will be randomized on Day 1 of Treatment Period 1 to receive either a single 12 mg dose of perampanel IV infusion (90-minute duration) or a single 12 mg oral tablet after an overnight fast. Participants will then receive the alternative treatment on Day 43 of Treatment Period 2. Drug administration will be separated by a washout of at least 6 weeks between the 2 treatment periods.
干预措施: Perampanel (Drug)
结局指标
主要结局
Mean maximum observed concentration (Cmax) postdose of perampanel
时间窗: predose; 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, and 12 (Day [D]1 and D43); 24 and 36 (D2 and D44); 48 (D3 and D45); 72 (D4 and D46); 120 (D6 and D48); 168 (D8 and D50); 336 (D15 and D57); and 504 (D22 and D64) hours after dosing start
Cmax is the maximum plasma concentration of a drug after administration. Dosing will occur on Day 1 of Treatment Period 1 and Day 43 of Treatment Period 2.
Mean value for area under the concentration versus time curve from time 0 to time of last measurable concentration (AUC[0-t]) postdose of perampanel
时间窗: predose; 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, and 12 (D1 and D43); 24 and 36 (D2 and D44); 48 (D3 and D45); 72 (D4 and D46); 120 (D6 and D48); 168 (D8 and D50); 336 (D15 and D57); and 504 (D22 and D64) hours after dosing start
AUC is a measure of actual body exposure to drug after administration of the drug. Dosing will occur on Day 1 of Treatment Period 1 and Day 43 of Treatment Period 2.
Mean value for AUC versus time curve from time 0 to infinity (AUC[0-inf]) postdose of perampanel
时间窗: predose; 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, and 12 (D1 and D43); 24 and 36 (D2 and D44); 48 (D3 and D45); 72 (D4 and D46); 120 (D6 and D48); 168 (D8 and D50); 336 (D15 and D57); and 504 (D22 and D64) hours after dosing start
AUC is a measure of actual body exposure to drug after administration of the drug. Dosing will occur on Day 1 of Treatment Period 1 and Day 43 of Treatment Period 2.
次要结局
- Mean total clearance (CL) post intravenous (IV) infusion of perampanel(predose; 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, and 12 (D1 and D43); 24 and 36 (D2 and D44); 48 (D3 and D45); 72 (D4 and D46); 120 (D6 and D48); 168 (D8 and D50); 336 (D15 and D57); and 504 (D22 and D64) hours after dosing start)
- Mean value for AUC versus time curve from time 0 to 72 hours (AUC[0-72h]) postdose of perampanel(predose; 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, and 12 (D1 and D43); 24 and 36 (D2 and D44); 48 (D3 and D45); 72 (D4 and D46); 120 (D6 and D48); 168 (D8 and D50); 336 (D15 and D57); and 504 (D22 and D64) hours after dosing start)
- Mean time to reach maximum concentration (tmax) postdose of perampanel(predose; 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, and 12 (D1 and D43); 24 and 36 (D2 and D44); 48 (D3 and D45); 72 (D4 and D46); 120 (D6 and D48); 168 (D8 and D50); 336 (D15 and D57); and 504 (D22 and D64) hours after dosing start)
- Mean terminal phase half-life (t1/2) postdose of perampanel(predose; 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, and 12 (D1 and D43); 24 and 36 (D2 and D44); 48 (D3 and D45); 72 (D4 and D46); 120 (D6 and D48); 168 (D8 and D50); 336 (D15 and D57); and 504 (D22 and D64) hours after dosing start)
- Number of participants with any treatment-emergent (TE) serious adverse event (SAE)(Up to approximately 16 weeks)
- Mean volume of distribution (Vd) post IV infusion of perampanel(predose; 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, and 12 (D1 and D43); 24 and 36 (D2 and D44); 48 (D3 and D45); 72 (D4 and D46); 120 (D6 and D48); 168 (D8 and D50); 336 (D15 and D57); and 504 (D22 and D64) hours after dosing start)
- Number of participants requiring concomitant medication(Up to approximately 16 weeks)
- Number of participants with any non-serious TEAE(Up to approximately 16 weeks)
- Number of participants with an abnormal, clinically significant physical examination finding(Up to approximately 16 weeks)
- Number of participants with an abnormal, clinically significant laboratory parameter value(Up to approximately 16 weeks)
- Number of participants with an abnormal, clinically significant vital sign value(Up to approximately 16 weeks)