KF2024#1-trial: Esketamine Interaction Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Area under the plasma concentration - time curve of esketamine
研究概览
简要总结
Esketamine is a drug which is used for depression treatment, to relieve pain and, in larger doses, in anesthesia. Spravato nasal spray is the only esketamine product on the market used for the treatment of depression, but the high price limits the use of the drug.
The aim of this study is to compare the concentration of esketamine after nasal (licensed product Spravato) and oral administration with and without a CYP3A4 inhibitor. Grapefruit juice and cobicistat are studied as CYP3A4 inhibitors in the study.
In an open four-phase, randomized, alternating study with 12 healthy volunteers, the subjects will receive Spravato 28 mg nasal or esketamine 28 mg oral with either grapefruit juice, cobicistat or water in the study facilities. Blood samples will be collected and esketamine pharmacokinetics will be monitored up to 24 hours postdose. Primary endpoint is area under the plasma concentration-time curve of esketamine.
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 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •signed consent
- •age 18-45 years
- •no indications of substance abuse
- •Accepted results from laboratory tests (blood hemoglobin, basic blood count and blood platelets, alanine aminotransferase, alkaline phosphatase, glutamyl transferase, creatinine, plasma potassium and sodium). Negative pregnancy test result (serum human chorionic gonadotropin) for women.
- •no significant abnormalities in the ECG
- •systolic blood pressure 140 mmHg-100 mmHg
- •heart rate ≥50/minute
排除标准
- •significant illness
- •less than 3 months since the last clinical trial
- •less than 3 months after donating blood
- •significant overweight/poor veins
- •BMI below 18.5 kg/m2
- •past or present mood disorder or suicidality
- •substance abuse
- •systolic blood pressure below 100 mmHg or above 140 mmHg
- •heart rate <50/minute
- •conduction disorder or other significant abnormality in the ECG
- •regular medication (including e-pills and other preparations containing estrogens)
- •pregnancy or its planning or breastfeeding
- •hypersensitivity to investigational drugs or excipients of medicinal products
- •use of natural products (such as St. John's wort)
研究组 & 干预措施
Esketamine Nasal Spray
250 ml water at 8.00 and 9.00 a.m. on the study day. Study drug dose (Esketamine Spravato, 28 mg) nasally at 9.00 a.m. on the study day.
干预措施: Esketamine Nasal Spray (Drug)
Esketamine p.o. and water
250 ml water at 8.00 and 9.00 a.m. on the study day. Study drug dose (Esketamine Kalceks 5 mg/ml, 28 mg) p.o. at 9.00 a.m. on the study day.
干预措施: Esketamine 28 mg (Drug)
Esketamine p.o. and grapefruit juice
250 ml grapefruit juice at 8.00 and 9.00 a.m. on the study day. Study drug dose (Esketamine Kalceks 5 mg/ml, 28 mg) p.o. at 9.00 a.m. on the study day.
干预措施: Esketamine 28 mg (Drug)
Esketamine p.o. and Cobisistat
150 mg Cobisistat and 250 ml water at 8.00 a.m. on the study day. Study drug dose (Esketamine Kalceks 5 mg/ml, 28 mg) p.o. and 250 ml water at 9.00 a.m. on the study day.
干预措施: Esketamine 28 mg (Drug)
Esketamine p.o. and Cobisistat
150 mg Cobisistat and 250 ml water at 8.00 a.m. on the study day. Study drug dose (Esketamine Kalceks 5 mg/ml, 28 mg) p.o. and 250 ml water at 9.00 a.m. on the study day.
干预措施: Cobicistat 150 MG (Drug)
Esketamine p.o. and grapefruit juice
250 ml grapefruit juice at 8.00 and 9.00 a.m. on the study day. Study drug dose (Esketamine Kalceks 5 mg/ml, 28 mg) p.o. at 9.00 a.m. on the study day.
干预措施: Grapefruit juice (Other)
结局指标
主要结局
Area under the plasma concentration - time curve of esketamine
时间窗: Prior to and 10, 20, 30, 40, 50, 60, 75, 90, 105 minutes and 2 , 3, 4, 6, 8, 10, 12 and 24 hours after administration the drug.
次要结局
- Peak plasma concentration for both esketamine and its metabolites(Prior to and 10, 20, 30, 40, 50, 60, 75, 90, 105 minutes and 2 , 3, 4, 6, 8, 10, 12 and 24 hours after administration the drug.)
- Half-life for both esketamine and its metabolites(Prior to and 10, 20, 30, 40, 50, 60, 75, 90, 105 minutes and 2 , 3, 4, 6, 8, 10, 12 and 24 hours after administration the drug.)
- Time to peak plasma concentration for both esketamine and its metabolites(Prior to and 10, 20, 30, 40, 50, 60, 75, 90, 105 minutes and 2 , 3, 4, 6, 8, 10, 12 and 24 hours after administration the drug.)
- Fractional areas under concentration-time curve (AUC) for both esketamine and its metabolites(Prior to and 10, 20, 30, 40, 50, 60, 75, 90, 105 minutes and 2 , 3, 4, 6, 8, 10, 12 and 24 hours after administration the drug.)
- Areas under concentration-time curve (AUC) for esketamine metabolites(Prior to and 10, 20, 30, 40, 50, 60, 75, 90, 105 minutes and 2 , 3, 4, 6, 8, 10, 12 and 24 hours after administration the drug.)
- Blood pressure(0, 60, 120 and 240 minutes after administration)
- Heart rate(0, 60, 120 and 240 minutes after administration)
研究者
Janne Backman
Professor
Helsinki University Central Hospital