Bioequivalence of Three Different Tablet Formulations of 30 mg of Apremilast (EU-sourced Otezla® vs. US-sourced Otezla® vs. Japan-sourced Otezla®) Administered in Healthy Male and Female Subjects in the Fasted State as Well as (for EU-sourced Otezla® vs. US-sourced Otezla®) in the Fed State (an Open-label, Randomised, Single-dose, Five-period, Ten-sequence Crossover Study)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Area Under the Concentration-time Curve of Apremilast in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
研究概览
简要总结
The aim of this trial is to establish bioequivalence between EU-, US- and Japan-sourced Otezla® tablet formulations to assure comparability of results from Phase III trials of BI 730357 (new oral agent for treatment of psoriasis as well as other T helper 17 cells (Th17)-mediated diseases) regardless of whether only the EU-sourced Otezla® or EU and US-sourced Otezla®/Japan-sourced Otezla® have been used as an active comparator.
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
- •Healthy male or female subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (Blood pressure (BP), Pulse rate (PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests
- •Age of 18 to 55 years (inclusive)
- •Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive)
- •Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation
- •Male subjects, or female subjects who meet any of the following criteria for a highly effective contraception from at least 30 days before the first administration of trial medication until 30 days after trial completion:
- •Use of combined (estrogen and progestogen containing) hormonal contraception that prevents ovulation (oral, intravaginal or transdermal), plus condom
- •Use of progestogen-only hormonal contraception that inhibits ovulation (only injectables or implants), plus condom
- •Use of intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)
- •A vasectomised sexual partner (vasectomy at least 1 year prior to enrolment)
- •Surgically sterilised (including hysterectomy or bilateral occlusion)
- •Postmenopausal, defined as no menses for 1 year without an alternative medical cause (in questionable cases a blood sample with levels of Follicle-stimulating hormone (FSH) above 40 U/L and estradiol below 30 ng/L is confirmatory)
排除标准
- •Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator
- •Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 bpm
- •Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
- •Any evidence of a concomitant disease assessed as clinically relevant by the investigator
- •Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
- •Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
- •Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
- •History of relevant orthostatic hypotension, fainting spells, or blackouts Further exclusion criteria apply.
研究组 & 干预措施
EU-Otezla fasted(A)/ Japan-Otezla fasted(E)/ US-Otezla fasted(B)/ US-Otezla fed(D)/ EU-Otezla fed(C)
Treatment sequence AEBDC is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: EU-sourced Otezla® (Drug)
EU-Otezla fasted(A)/ Japan-Otezla fasted(E)/ US-Otezla fasted(B)/ US-Otezla fed(D)/ EU-Otezla fed(C)
Treatment sequence AEBDC is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: US-sourced Otezla® (Drug)
EU-Otezla fasted(A)/ Japan-Otezla fasted(E)/ US-Otezla fasted(B)/ US-Otezla fed(D)/ EU-Otezla fed(C)
Treatment sequence AEBDC is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: Japan-sourced Otezla® (Drug)
US-Otezla fasted(B)/ EU-Otezla fasted(A)/ EU-Otezla fed(C)/ Japan-Otezla fasted(E)/ US-Otezla fed(D)
Treatment sequence BACED is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: EU-sourced Otezla® (Drug)
US-Otezla fasted(B)/ EU-Otezla fasted(A)/ EU-Otezla fed(C)/ Japan-Otezla fasted(E)/ US-Otezla fed(D)
Treatment sequence BACED is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: Japan-sourced Otezla® (Drug)
US-Otezla fasted(B)/ EU-Otezla fasted(A)/ EU-Otezla fed(C)/ Japan-Otezla fasted(E)/ US-Otezla fed(D)
Treatment sequence BACED is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: US-sourced Otezla® (Drug)
EU-Otezla fed(C)/US-Otezla fasted(B)/US-Otezla fasted(D)/EU-Otezla fasted(A)/ Japan-Otezla fasted(E)
Treatment sequence CBDAE is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: EU-sourced Otezla® (Drug)
EU-Otezla fed(C)/US-Otezla fasted(B)/US-Otezla fasted(D)/EU-Otezla fasted(A)/ Japan-Otezla fasted(E)
Treatment sequence CBDAE is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: US-sourced Otezla® (Drug)
EU-Otezla fed(C)/US-Otezla fasted(B)/US-Otezla fasted(D)/EU-Otezla fasted(A)/ Japan-Otezla fasted(E)
Treatment sequence CBDAE is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: Japan-sourced Otezla® (Drug)
US-Otezla fed(D)/ EU-Otezla fed(C)/ Japan-Otezla fasted(E)/ US-Otezla fasted(B)/ EU-Otezla fasted(A)
Treatment sequence DCEAB is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: EU-sourced Otezla® (Drug)
US-Otezla fed(D)/ EU-Otezla fed(C)/ Japan-Otezla fasted(E)/ US-Otezla fasted(B)/ EU-Otezla fasted(A)
Treatment sequence DCEAB is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: US-sourced Otezla® (Drug)
US-Otezla fed(D)/ EU-Otezla fed(C)/ Japan-Otezla fasted(E)/ US-Otezla fasted(B)/ EU-Otezla fasted(A)
Treatment sequence DCEAB is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: Japan-sourced Otezla® (Drug)
Japan-Otezla fasted(E)/ US-Otezla fed(D)/ EU-Otezla fasted(A)/EU-Otezla fed(C)/ US-Otezla fasted(B)
Treatment sequence EDACB is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: EU-sourced Otezla® (Drug)
Japan-Otezla fasted(E)/ US-Otezla fed(D)/ EU-Otezla fasted(A)/EU-Otezla fed(C)/ US-Otezla fasted(B)
Treatment sequence EDACB is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: US-sourced Otezla® (Drug)
Japan-Otezla fasted(E)/ US-Otezla fed(D)/ EU-Otezla fasted(A)/EU-Otezla fed(C)/ US-Otezla fasted(B)
Treatment sequence EDACB is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: Japan-sourced Otezla® (Drug)
EU-Otezla fasted(A)/ US-Otezla fasted(B)/ Japan-Otezla fasted(E)/ EU-Otezla fed(C)/ US-Otezla fed(D)
Treatment sequence ABECD is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: EU-sourced Otezla® (Drug)
EU-Otezla fasted(A)/ US-Otezla fasted(B)/ Japan-Otezla fasted(E)/ EU-Otezla fed(C)/ US-Otezla fed(D)
Treatment sequence ABECD is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: US-sourced Otezla® (Drug)
EU-Otezla fasted(A)/ US-Otezla fasted(B)/ Japan-Otezla fasted(E)/ EU-Otezla fed(C)/ US-Otezla fed(D)
Treatment sequence ABECD is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: Japan-sourced Otezla® (Drug)
US-Otezla fasted(B)/ EU-Otezla fed(C)/ EU-Otezla fasted(A)/ US-Otezla fed(D)/ Japan-Otezla fasted(E)
Treatment sequence BCADE is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: EU-sourced Otezla® (Drug)
US-Otezla fasted(B)/ EU-Otezla fed(C)/ EU-Otezla fasted(A)/ US-Otezla fed(D)/ Japan-Otezla fasted(E)
Treatment sequence BCADE is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: US-sourced Otezla® (Drug)
US-Otezla fasted(B)/ EU-Otezla fed(C)/ EU-Otezla fasted(A)/ US-Otezla fed(D)/ Japan-Otezla fasted(E)
Treatment sequence BCADE is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: Japan-sourced Otezla® (Drug)
EU-Otezla fed(C)/ US-Otezla fed(D)/ US-Otezla fasted(B)/ Japan-Otezla fasted(E)/ EU-Otezla fasted(A)
Treatment sequence CDBEA is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: EU-sourced Otezla® (Drug)
EU-Otezla fed(C)/ US-Otezla fed(D)/ US-Otezla fasted(B)/ Japan-Otezla fasted(E)/ EU-Otezla fasted(A)
Treatment sequence CDBEA is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: US-sourced Otezla® (Drug)
EU-Otezla fed(C)/ US-Otezla fed(D)/ US-Otezla fasted(B)/ Japan-Otezla fasted(E)/ EU-Otezla fasted(A)
Treatment sequence CDBEA is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: Japan-sourced Otezla® (Drug)
US-Otezla fed(D)/ Japan-Otezla fasted(E)/ EU-Otezla fed(C)/ EU-Otezla fasted(A)/ US-Otezla fasted(B)
Treatment sequence DECAB is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: EU-sourced Otezla® (Drug)
US-Otezla fed(D)/ Japan-Otezla fasted(E)/ EU-Otezla fed(C)/ EU-Otezla fasted(A)/ US-Otezla fasted(B)
Treatment sequence DECAB is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: US-sourced Otezla® (Drug)
US-Otezla fed(D)/ Japan-Otezla fasted(E)/ EU-Otezla fed(C)/ EU-Otezla fasted(A)/ US-Otezla fasted(B)
Treatment sequence DECAB is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: Japan-sourced Otezla® (Drug)
Japan-Otezla fasted(E)/ EU-Otezla fasted(A)/ US-Otezla fed(D)/ US-Otezla fasted(B)/ EU-Otezla fed(C)
Treatment sequence EADBC is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: EU-sourced Otezla® (Drug)
Japan-Otezla fasted(E)/ EU-Otezla fasted(A)/ US-Otezla fed(D)/ US-Otezla fasted(B)/ EU-Otezla fed(C)
Treatment sequence EADBC is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: US-sourced Otezla® (Drug)
Japan-Otezla fasted(E)/ EU-Otezla fasted(A)/ US-Otezla fed(D)/ US-Otezla fasted(B)/ EU-Otezla fed(C)
Treatment sequence EADBC is applied. The 5 treatments were separated by a washout period of at least 5 days.
干预措施: Japan-sourced Otezla® (Drug)
结局指标
主要结局
Area Under the Concentration-time Curve of Apremilast in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
时间窗: 1 hour (h) before and 30 minutes (min), 1h, 1h30min, 2h, 2h30min, 3h, 3h30min, 4h, 5h, 6h, 8h, 11h, 15h, 24h, 36h, 48h after study drug administration.
The area under the concentration-time curve of apremilast in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported.
Area Under the Concentration-time Curve of Apremilast in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
时间窗: 1 hour (h) before and 30 minutes (min), 1h, 1h30min, 2h, 2h30min, 3h, 3h30min, 4h, 5h, 6h, 8h, 11h, 15h, 24h, 36h, 48h after study drug administration.
The area under the concentration-time curve of apremilast in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported.
Maximum Measured Concentration of Apremilast in Plasma (Cmax)
时间窗: 1 hour (h) before and 30 minutes (min), 1h, 1h30min, 2h, 2h30min, 3h, 3h30min, 4h, 5h, 6h, 8h, 11h, 15h, 24h, 36h, 48h after study drug administration.
The maximum measured concentration of apremilast in plasma (Cmax) is reported.
次要结局
未报告次要终点