A Randomized, 3-Treatment, 3-Period, 6-Sequence, Crossover, Placebo- and Active-Controlled, Double-Blind for ALXN1840 (Open-Label for Moxifloxacin) Thorough QT/QTc Study to Evaluate ALXN1840 on Cardiac Repolarization in Healthy Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 57
- 试验地点
- 1
- 主要终点
- Placebo-corrected Change From Baseline For QTcF (ΔΔQTcF) for ALXN1840 Using The By-time Point Analysis
研究概览
简要总结
This study will evaluate the effect of a supratherapeutic dose of ALXN1840 on the heart rate (HR)-corrected QT interval (QTc) in healthy adult participants. Moxifloxacin will be used as the active control.
详细描述
This is a randomized, 3-treatment, 3-period, 6-sequence, crossover, placebo- and active-controlled, double-blind for ALXN1840, open-label for moxifloxacin, in healthy adult participants. Participants will be domiciled in the clinic for 7 days during Treatment Period 1 and for 6 days during Treatment Period 2 and 3. A single oral dose of each treatment (ALXN1840, matching ALXN1840 placebo, or moxifloxacin) will be administered on Day 1 of each period following an overnight fast of at least 10 hours. There will be a minimum 14-day washout between study intervention administrations for each treatment period. Cardiodynamic, pharmacokinetic, and safety assessments will be performed at certain times during the study. An end-of-study visit will occur 14 days (±2 days) after the last dose.
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
- Double (Participant, Care Provider)
盲法说明
This study will employ a double-blind study design. The ALXN1840 and matching placebo will be identical in appearance and will be administered in a double-blind manner.
Moxifloxacin will not be blinded.
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
- •Body weight at least 60 kilograms (kg) for males or 52 kg for females and body mass index ≥18.0 and ≤30.0 kg/meter squared.
- •Willing and able to follow protocol-specified contraception requirements.
- •Participant has no clinically significant history or presence of ECG findings.
排除标准
- •History or presence of clinical and/or lab disorders.
- •Lymphoma, leukemia, or any malignancy within the past 5 years, or breast cancer within the past 10 years.
- •Participant has abnormal blood pressure, defined as a supine blood pressure <90/50 millimeters of mercury (mm Hg) or >140/90 mm Hg.
- •Serum potassium, calcium, or magnesium levels outside the normal range.
- •Serum copper and/or ceruloplasmin values below the lower limit of normal at Screening.
- •Female participant has hemoglobin <10.8 grams/deciliter (g/dL) and male participant has hemoglobin <12.5 g/dL.
- •Clinically significant multiple or severe allergies.
- •Alanine aminotransferase, aspartate aminotransferase, serum creatinine, or total bilirubin greater than upper limit of normal (with the exception of Gilbert's syndrome).
研究组 & 干预措施
Treatment Sequence 1
On Day 1 of each period, participants will receive a single dose of the following study interventions:
Period 1: ALXN1840.
Period 2: Placebo-matching ALXN1840.
Period 3: Moxifloxacin.
干预措施: ALXN1840 (Drug)
Treatment Sequence 1
On Day 1 of each period, participants will receive a single dose of the following study interventions:
Period 1: ALXN1840.
Period 2: Placebo-matching ALXN1840.
Period 3: Moxifloxacin.
干预措施: Placebo (Drug)
Treatment Sequence 1
On Day 1 of each period, participants will receive a single dose of the following study interventions:
Period 1: ALXN1840.
Period 2: Placebo-matching ALXN1840.
Period 3: Moxifloxacin.
干预措施: Moxifloxacin (Drug)
Treatment Sequence 3
On Day 1 of each period, participants will receive a single dose of the following study interventions:
Period 1: Placebo-matching ALXN1840.
Period 2: ALXN1840.
Period 3: Moxifloxacin.
干预措施: Moxifloxacin (Drug)
Treatment Sequence 2
On Day 1 of each period, participants will receive a single dose of the following study interventions:
Period 1: ALXN1840.
Period 2: Moxifloxacin.
Period 3: Placebo-matching ALXN1840.
干预措施: ALXN1840 (Drug)
Treatment Sequence 2
On Day 1 of each period, participants will receive a single dose of the following study interventions:
Period 1: ALXN1840.
Period 2: Moxifloxacin.
Period 3: Placebo-matching ALXN1840.
干预措施: Placebo (Drug)
Treatment Sequence 2
On Day 1 of each period, participants will receive a single dose of the following study interventions:
Period 1: ALXN1840.
Period 2: Moxifloxacin.
Period 3: Placebo-matching ALXN1840.
干预措施: Moxifloxacin (Drug)
Treatment Sequence 3
On Day 1 of each period, participants will receive a single dose of the following study interventions:
Period 1: Placebo-matching ALXN1840.
Period 2: ALXN1840.
Period 3: Moxifloxacin.
干预措施: ALXN1840 (Drug)
Treatment Sequence 3
On Day 1 of each period, participants will receive a single dose of the following study interventions:
Period 1: Placebo-matching ALXN1840.
Period 2: ALXN1840.
Period 3: Moxifloxacin.
干预措施: Placebo (Drug)
Treatment Sequence 4
On Day 1 of each period, participants will receive a single dose of the following study interventions:
Period 1: Placebo-matching ALXN1840.
Period 2: Moxifloxacin.
Period 3: ALXN1840.
干预措施: ALXN1840 (Drug)
Treatment Sequence 4
On Day 1 of each period, participants will receive a single dose of the following study interventions:
Period 1: Placebo-matching ALXN1840.
Period 2: Moxifloxacin.
Period 3: ALXN1840.
干预措施: Placebo (Drug)
Treatment Sequence 4
On Day 1 of each period, participants will receive a single dose of the following study interventions:
Period 1: Placebo-matching ALXN1840.
Period 2: Moxifloxacin.
Period 3: ALXN1840.
干预措施: Moxifloxacin (Drug)
Treatment Sequence 5
On Day 1 of each period, participants will receive a single dose of the following study interventions:
Period 1: Moxifloxacin.
Period 2: ALXN1840.
Period 3: Placebo-matching ALXN1840.
干预措施: ALXN1840 (Drug)
Treatment Sequence 5
On Day 1 of each period, participants will receive a single dose of the following study interventions:
Period 1: Moxifloxacin.
Period 2: ALXN1840.
Period 3: Placebo-matching ALXN1840.
干预措施: Placebo (Drug)
Treatment Sequence 5
On Day 1 of each period, participants will receive a single dose of the following study interventions:
Period 1: Moxifloxacin.
Period 2: ALXN1840.
Period 3: Placebo-matching ALXN1840.
干预措施: Moxifloxacin (Drug)
Treatment Sequence 6
On Day 1 of each period, participants will receive a single dose of the following study interventions:
Period 1: Moxifloxacin.
Period 2: Placebo-matching ALXN1840.
Period 3: ALXN1840.
干预措施: ALXN1840 (Drug)
Treatment Sequence 6
On Day 1 of each period, participants will receive a single dose of the following study interventions:
Period 1: Moxifloxacin.
Period 2: Placebo-matching ALXN1840.
Period 3: ALXN1840.
干预措施: Placebo (Drug)
Treatment Sequence 6
On Day 1 of each period, participants will receive a single dose of the following study interventions:
Period 1: Moxifloxacin.
Period 2: Placebo-matching ALXN1840.
Period 3: ALXN1840.
干预措施: Moxifloxacin (Drug)
结局指标
主要结局
Placebo-corrected Change From Baseline For QTcF (ΔΔQTcF) for ALXN1840 Using The By-time Point Analysis
时间窗: Baseline (average of samples taken at -45, -30, and -15 minutes before dosing), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 (Day 2) hours postdose
Twelve-lead electrocardiograms (ECGs) were extracted from approximately 25-hour continuous (Holter) recordings on Day -1 of Treatment Period 1 and Days 1 and 2 in each treatment period. Change from baseline in the QT interval was corrected for heart rate using Fridericia's formula (ΔQTcF). ΔQTcF was based on a mixed-effects model for repeated measures (MMRM) with ΔQTcF as the dependent variable; period, sequence, time, treatment, and time-by-treatment interaction as fixed effects; and baseline QTc and sex as covariates. ΔΔQTc = LS mean ΔQTcF after ALXN1840 dosing minus LS mean ΔQTcF after placebo. If the upper bound of the confidence interval (CI) of ΔΔQTcF was \< 10 ms for all postdose time points, ALXN1840 was concluded to not have a significant effect on QT interval prolongation.
次要结局
- ΔΔQTcF For Moxifloxacin Using The By-time Point Analysis(1, 2, and 3 hours postdose at Day 1)
- Change From Baseline QRS Interval (ΔQRS)(Baseline (average of samples taken at 45, -30, and -15 minutes before dosing), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 (Day 2) hours postdose)
- Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS)(Baseline (average of samples taken at 45, -30, and -15 minutes before dosing), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 (Day 2) hours postdose)
- ALXN1840 PK Parameter: Time To Maximum Observed Concentration (Tmax) Of Total Molybdenum And PUF Molybdenum Following a Single Oral Dose of ALXN1840(Pre-dose to 96 hours post-dose)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(Day 1 (after dosing) through Day 70)
- Change From Baseline For Heart Rate (ΔHR)(Baseline (average of samples taken at 45, -30, and -15 minutes before dosing), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 (Day 2) hours postdose)
- Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF)(Baseline (average of samples taken at 45, -30, and -15 minutes before dosing), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 (Day 2) hours postdose)
- Change From Baseline PR Interval (ΔPR)(Baseline (average of samples taken at 45, -30, and -15 minutes before dosing), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 (Day 2) hours postdose)
- Placebo-corrected Change From Baseline PR Interval (ΔΔPR)(Baseline (average of samples taken at 45, -30, and -15 minutes before dosing), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 (Day 2) hours postdose)
- Number of Participants With Treatment-emergent T-wave Morphology Abnormalities and U-waves(Day 1 (after dosing) through 24 hours postdose)
- ALXN1840 PK Parameter: Area Under The Concentration Versus Time Curve From Time 0 To The Last Quantifiable Concentration (AUC0-t) Of Total Molybdenum And Plasma Ultrafiltrate (PUF) Molybdenum Following a Single Oral Dose of ALXN1840(Predose (0) to 96 hours post-dose)
- ALXN1840 PK Parameter: Maximum Observed Concentration (Cmax) Of Total Molybdenum And PUF Molybdenum Following a Single Oral Dose of ALXN1840(Predose (0) to 96 hours post-dose)
- Placebo-corrected Change From Baseline Heart Rate (ΔΔHR)(Baseline (average of samples taken at 45, -30, and -15 minutes before dosing), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 (Day 2) hours postdose)