Bioequivalence of Zongertinib Tablets From Two Different Manufacturers Following Oral Administration in Healthy Male and Female Subjects (an Open-label, Randomised, Single-dose, Two-period, Two-sequence Crossover Trial)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Area Under the Concentration-time Curve of Zongertinib in Plasma Over the Time Interval From 0 to 72h (AUC0-72h)
研究概览
简要总结
The main objective of this trial is to establish the bioequivalence of zongertinib tablet from manufacturer 1 (Test, T) compared with zongertinib tablet from manufacturer 2 (reference, R) following oral administration.
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 50 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 50 years (inclusive)
- •BMI (Body mass index) of 18.5 to 29.9 kg/m2 (inclusive)
- •Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial
- •Either male subject, or female subject 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 progestogen-only hormonal contraception that inhibits ovulation (only injectables or implants), plus condom
- •Use of intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)
- •Sexually abstinent
- •A vasectomised sexual partner who received medical assessment of the surgical success (documented absence of sperm) and provided that partner is the sole sexual partner of the trial participant
- •Surgically sterilised (including hysterectomy or bilateral tubular 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 50 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
Zongertinib (manufacturer 1) Test followed by zongertinb (manufacturer 2) Reference treatment (T-R)
Participants were administered during Period 1 on Day 1 a single oral dose of 60 milligrams (mg) of zongertinib film-coated tablet produced by Manufacturer 1 (Test treatment, T) with 240 milliliters (ml) of water following an overnight fast of at least 10 hours (hrs). Following a washout period of at least 14 days, participants were administered a single oral dose of 60 mg of zongertinib produced by Manufacturer 2 (Reference treatment, R) with 240 mL of water after an overnight fast of at least 10 hrs.
干预措施: Zongertinib manufacturer 1 (Drug)
Zongertinib (manufacturer 1) Test followed by zongertinb (manufacturer 2) Reference treatment (T-R)
Participants were administered during Period 1 on Day 1 a single oral dose of 60 milligrams (mg) of zongertinib film-coated tablet produced by Manufacturer 1 (Test treatment, T) with 240 milliliters (ml) of water following an overnight fast of at least 10 hours (hrs). Following a washout period of at least 14 days, participants were administered a single oral dose of 60 mg of zongertinib produced by Manufacturer 2 (Reference treatment, R) with 240 mL of water after an overnight fast of at least 10 hrs.
干预措施: Zongertinib manufacturer 2 (Drug)
Zongertinib (manufacturer 2) Reference followed by zongertinb (manufacturer 1) Test treatment (R-T)
Participants were administered during Period 1 on Day 1 a single oral dose of 60 mg of zongertinib film-coated tablet produced by Manufacturer 2 (Reference treatment, R) with 240 ml of water following an overnight fast of at least 10 hrs. Following a washout period of at least 14 days, participants were administered a single oral dose of 60 mg of zongertinib produced by Manufacturer 1 (Test treatment, T) with 240 mL of water after an overnight fast of at least 10 hrs.
干预措施: Zongertinib manufacturer 1 (Drug)
Zongertinib (manufacturer 2) Reference followed by zongertinb (manufacturer 1) Test treatment (R-T)
Participants were administered during Period 1 on Day 1 a single oral dose of 60 mg of zongertinib film-coated tablet produced by Manufacturer 2 (Reference treatment, R) with 240 ml of water following an overnight fast of at least 10 hrs. Following a washout period of at least 14 days, participants were administered a single oral dose of 60 mg of zongertinib produced by Manufacturer 1 (Test treatment, T) with 240 mL of water after an overnight fast of at least 10 hrs.
干预措施: Zongertinib manufacturer 2 (Drug)
结局指标
主要结局
Area Under the Concentration-time Curve of Zongertinib in Plasma Over the Time Interval From 0 to 72h (AUC0-72h)
时间窗: Within 3 hours prior to and 0.50, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours after administration of zongertinib Test Treatment and zongertinib Reference Treatment.
Area under the concentration-time curve of zongertinib in plasma over the time interval from 0 to 72h (AUC0-72h) is reported. Geometric least squares mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance model (ANOVA) on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. The model included 'subjects within sequences' as a random effect, and sequence, period and treatment as fixed. These quantities were then back transformed to the original scale to provide the point estimate and 90% confidence intervals (CIs) for each endpoint.
Maximum Measured Concentration of Zongertinib in Plasma (Cmax)
时间窗: Within 3 hours prior to and 0.50, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours after administration of zongertinib Test Treatment and zongertinib Reference Treatment.
Maximum measured concentration of zongertinib in plasma (Cmax) is reported. Geometric least squares mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance model (ANOVA) on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. The model included 'subjects within sequences' as a random effect, and sequence, period and treatment as fixed. These quantities were then back transformed to the original scale to provide the point estimate and 90% confidence intervals (CIs) for each endpoint.
次要结局
- Time From Dosing to Maximum Measured Concentration of Zongertinib in Plasma (Tmax)(Within 3 hours prior to and 0.50, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours after administration of zongertinib Test Treatment and zongertinib Reference Treatment.)