A Phase 1, Randomized, 2-Period, 2-Sequence, Cross-over Study to Determine the Effect of ALXN1840 on the Metabolism of a CYP2C9 Substrate in Healthy Participants.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Maximum Observed Plasma Concentration (Cmax) Of Celecoxib With And Without The Coadministration Of ALXN1840
研究概览
简要总结
This was a Phase 1, randomized, 2-period, 2-sequence, cross-over study designed to determine the effect of ALXN1840 on the metabolism of celecoxib, a sensitive cytochrome P450 2C9 (CYP2C9) substrate, in healthy male and female participants. The safety and tolerability of ALXN1840 were determined along with ALXN1840 pharmacokinetics (PK) in plasma as measured via total molybdenum with the coadministration of celecoxib.
详细描述
The study was conducted as a randomized, 2-period, 2-sequence, cross-over study to determine the effect of a single dose of ALXN1840 (perpetrator) on the single-dose celecoxib (victim) kinetics in healthy male and female participants.
The study had a Screening period (Day -28 to Day -2), two 11-day study periods (Day 1 to Day 11) with a minimum of 14 days between doses of celecoxib, and an End of Study Visit (Day 15 ± 2 days) after Period 2 dosing. Participants only reported to the clinical research unit (CRU) on the day prior to the first dose because they were kept in the CRU during the wash-out period due to coronavirus disease 2019.
All participants received a single dose of celecoxib alone (Treatment A) and celecoxib coadministered with ALXN1840 (Treatment B) during the study, 1 in each treatment period. Based on randomization, participants were administered either Treatments A-B or Treatments B-A in each study period.
The PK profile of ALXN1840 and celecoxib was determined by blood sampling following single-dose administration. In addition to PK sampling, safety and tolerability were assessed by monitoring adverse events, vital signs, 12-lead electrocardiograms, physical examinations, and laboratory parameters.
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
- •Adequate venous access in the left or right arm to allow the collection of blood samples.
- •Bodyweight ≥ 45 to ≤ 100 kilograms (kg) and body mass index within the range of 18 to < 30 kg/meter squared.
- •Willing and able to follow protocol-specified contraception requirements.
- •Capable of giving signed informed consent.
排除标准
- •History or presence of/significant medical history.
- •Clinically significant multiple or severe allergies.
- •Lymphoma, leukemia, or any malignancy within 5 years.
- •Breast cancer within the past 10 years.
- •Serum creatinine > upper limit of normal (ULN) of the reference range.
- •Alanine aminotransferase, aspartate aminotransferase, or total bilirubin > ULN.
- •Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- •QTc > 450 milliseconds (msec) for male participants or > 470 msec for female participants.
研究组 & 干预措施
Treatment Sequence A-B
Participants received 1 treatment during each study period in the following sequence:
- Treatment A: Celecoxib.
- Treatment B: Celecoxib plus ALXN1840.
干预措施: ALXN1840 (Drug)
Treatment Sequence A-B
Participants received 1 treatment during each study period in the following sequence:
- Treatment A: Celecoxib.
- Treatment B: Celecoxib plus ALXN1840.
干预措施: Celecoxib (Drug)
Treatment Sequence B-A
Participants received 1 treatment during each study period in the following sequence:
- Treatment B: Celecoxib plus ALXN1840.
- Treatment A: Celecoxib.
干预措施: ALXN1840 (Drug)
Treatment Sequence B-A
Participants received 1 treatment during each study period in the following sequence:
- Treatment B: Celecoxib plus ALXN1840.
- Treatment A: Celecoxib.
干预措施: Celecoxib (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax) Of Celecoxib With And Without The Coadministration Of ALXN1840
时间窗: Baseline, up to 336 hours post-dose
Blood samples were collected for pharmacokinetics (PK) analysis of celecoxib. Cmax is reported as nanograms (ng)/milliliter (mL).
Area Under The Plasma Concentration Versus Time Curve From Time 0 To The Last Quantifiable Concentration (AUCt) Of Celecoxib With And Without The Coadministration Of ALXN1840
时间窗: Baseline, up to 336 hours post-dose
Blood samples were collected for pharmacokinetic (PK) analysis of celecoxib. Area Under The Plasma Concentration Versus Time Curve From Time 0 To The Last Quantifiable Concentration (AUCt) is reported as hours•ng/mL (h•ng/mL).
Area Under The Plasma Concentration Versus Time Curve From Time 0 To Infinity (AUCinf) Of Celecoxib With And Without The Coadministration Of ALXN1840
时间窗: Baseline, up to 336 hours post-dose
Blood samples were collected for pharmacokinetic (PK) analysis of celecoxib. Area Under The Plasma Concentration Versus Time Curve From Time 0 To Infinity (AUCinf) is reported as h•ng/mL.
次要结局
- Cmax Of Molybdenum With Coadministration Of Celecoxib(Baseline, up to 336 hours post-dose)
- AUCinf Of Molybdenum With Coadministration Of Celecoxib(Baseline, up to 336 hours post-dose)
- AUCt Of Molybdenum With Coadministration Of Celecoxib(Baseline, up to 336 hours post-dose)