A Phase 1 Randomized, Open-Label, Two-Period,Two-Sequence Crossover Study to Evaluate the Relative Oral Bioavailability of Levoketoconazole and Ketoconazole Tablets in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Cortendo AB
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Ratio of geometric least squares means for AUClast of plasma levoketoconazole (2S,4R-ketoconazole)
研究概览
简要总结
This is a phase 1, randomized, open-label, single-dose, two-period, two-sequence crossover study in healthy male and female subjects to evaluate the relative oral bioavailability of levoketoconazole tablets (the test drug) and ketoconazole tablets (the reference drug product).
详细描述
This is a phase 1, randomized, open-label, single-dose, two-period, two-sequence crossover study in healthy male and female subjects to evaluate the relative oral bioavailability of levoketoconazole tablets (the test drug) and ketoconazole tablets (the reference drug product). Subjects will be randomized to receive a single oral dose of 150 mg levoketoconazole (Study Drug A) or a single oral dose of 200 mg ketoconazole (Study Drug B) in each period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 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
- •18 to 55 years of age, inclusive, at time of consent.
- •Body mass index (BMI) between 18.0 and 32.0 kg/m2,inclusive.
- •In good general physical health as determined by absence of clinically significant medical history, physical examination findings, vital signs, clinical laboratory evaluations, and ECG measurements.
- •Has not consumed and agrees to abstain from taking any prescription drugs, dietary supplements including vitamins and herbal preparations, or non-prescription drugs for 14 days prior to clinical research unit (CRU) admission, during washout period, and through Follow-Up.
- •Has not consumed alcohol-containing beverages for 3 days prior to CRU admission and agrees not to consume alcohol through Follow-Up.
- •Is a nonsmoker (for at least 3 months) with negative urinary cotinine test at Screening and agrees to abstain from tobacco-and nicotine-containing products for the duration of the study.
排除标准
- •Evidence of any out-of-normal-range laboratory value at Screening that has not been reviewed, approved, and documented as Not Clinically Significant by the Investigator.
- •Concurrent medical illness that would interfere with the conduct of the study in the opinion of the Investigator.
- •History or presence of clinically significant cardiovascular, pulmonary, hematologic, endocrine, immunologic, dermatologic, neurologic, psychiatric, renal, hepatic, chronic respiratory, or gastrointestinal disease as judged by the Investigator.
- •Positive urine drug screen for drugs-of-abuse, including cocaine, tetrahydrocannabinol, opioids, benzodiazepines, amphetamines, and barbiturates,and/or positive urine screen for alcohol at Screening and CRU admission.
- •Treatment with an investigational drug within the longer of 30 days or five half-lives of the investigational drug preceding the first dose of study drug.
- •Positive for HIV, hepatitis B, and/or hepatitis C on Screening assessments.
- •Acute illness within 7 days of CRU admission.
- •Donated plasma within 7 days of drug administration.
- •Donated 1 or more pints of blood (or equivalent blood loss) within 30 days prior to drug administration.
- •History of caffeine consumption exceeding 8 cups coffee/day within 14 days prior to first dose, or consumption of any caffeine-or chocolate-containing products for 3 days prior to CRU admission each week.
- •Female subjects who are pregnant or lactating.
- •Males with hemoglobin less than 12.0 g/dL at Screening or CRU admission; Females with hemoglobin less than 11.0 g/dL at Screening or CRU admission
- •Had difficulties with swallowing whole tablets.
- •Body habitus preventing repeated venipuncture as required by protocol.
研究组 & 干预措施
Levoketoconazole
Levoketoconazole 150 mg
干预措施: Levoketoconazole (Drug)
Ketoconazole
Ketoconazole 200 mg
干预措施: Ketoconazole (Drug)
结局指标
主要结局
Ratio of geometric least squares means for AUClast of plasma levoketoconazole (2S,4R-ketoconazole)
时间窗: 24 hours
Point estimates and 90 percent (%) confidence intervals (CIs) for the dose-normalized ratios of geometric least squares means between Test (levoketoconazole) and Reference (ketoconazole)
Ratio of geometric least squares means for AUCinf of plasma levoketoconazole (2S,4R-ketoconazole)
时间窗: 24 hours
Point estimates and 90 percent (%) confidence intervals (CIs) for the dose-normalized ratios of geometric least squares means between Test (levoketoconazole) and Reference (ketoconazole)
Ratio of geometric least squares means for Cmax of plasma levoketoconazole (2S,4R-ketoconazole)
时间窗: 24 hours
Point estimates and 90 percent (%) confidence intervals (CIs) for the dose-normalized ratios of geometric least squares means between Test (levoketoconazole) and Reference (ketoconazole)
次要结局
- Lag-time (Tlag)(24 hours)
- Incidence of adverse events (AEs)(35 days)
- Elimination half-life (T1/2)(24 hours)
- Terminal phase rate constant (λz)(24 hours)
- Apparent systemic clearance (CL/F)(24 hours)
- Volume of Distribution (Vz/F)(24 hours)
- Time to Maximum Plasma concentration (Tmax)(24 hours)
- The percentage of area under the plasma concentration-time curve extrapolated from time 0 to infinity as a percentage of total AUC (%AUCext)(24 hours)