A Randomized, Double-Blind, Placebo- and Active-Controlled, 3-Way Crossover Study in Healthy Subjects to Determine the Effect of Omaveloxolone on QTc Interval
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Biogen
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change from baseline in placebo-corrected QTcF (∆∆QTcF)
研究概览
简要总结
This is a randomized, double blind, placebo and active (moxifloxacin open label) controlled study in healthy subjects to assess the effect of the supratherapeutic exposure of omaveloxolone on QTc interval. Moxifloxacin will be used as an active control and will be administered as open label. Omaveloxolone and placebo will be administered in a blinded fashion. All treatments will be administered after an FDA high-fat meal. Concentration-QTc (C-QTc) analysis is the primary analysis for the study.
详细描述
Study Sponsor, originally Reata Pharmaceuticals, Inc., is now Reata Pharmaceuticals, Inc., a wholly owned subsidiary of Biogen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Care Provider, Investigator)
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 adult males and/or females, 18 to 55 years of age (inclusive) at the time of screening.
- •BMI at screening between 18.0 and 32.0 kg/m2 (inclusive)
- •Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception.
- •Able to comprehend and willing to sign an ICF and to abide by the study restrictions.
排除标准
- •History of clinically significant drug allergies, including allergies to any of the components of the study drugs (omaveloxolone and moxifloxacin) and/or clinically significant food allergies as determined by the investigator.
- •Subject has an ECG abnormality, including corrected QT interval (QTc)> 450 msec for males, and > 460 msec for females, HR < 45 bpm or > 100 bpm after 5 minutes in supine position, PR interval > 220 msec, or QRS interval > 110 msec.
- •Subject has allergy to band aids, adhesive dressing, or medical tape.
- •Subject has hypotension (systolic blood pressure blood pressure [BP] ≤ 90 mmHg, diastolic BP ≤ 50 mmHg), or hypertension (systolic BP ≥ 140 mmHg, diastolic BP ≥ 90 mmHg) at screening.
- •Subject has history of prolonged QTc, cardiac arrhythmia, or first-degree relatives with congenital Long QT syndrome or unexplained sudden death in young age.
- •Subject has a history of unstable angina, syncope, coronary artery disease, myocardial infarction, congestive heart failure (CHF), transient ischemic attack (TIA), or neurological disorder.
- •Presence or history of any significant cardiovascular, gastrointestinal, hepatic, renal, pulmonary, hematologic, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease, as determined by the investigator.
- •Presence of any other condition (including surgery) known to interfere with the absorption, distribution, metabolism, or excretion of medicines.
- •Requirement for any over the counter and/or prescription medication, vitamins, and/or herbal supplements on a regular basis
- •Use of any medications (over the counter and/or prescription medication), vitamins, and/or herbal supplements, within the 14-days prior to study drug administration or within 5 halflives (if known), whichever is longer
- •History of drug or alcohol abuse in the last 6 months as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition.
- •Positive test result for drugs of abuse, alcohol, or cotinine at screening or Day -
- •Positive test result for hepatitis B surface antigen, hepatitis C virus antibodies, or HIV antibodies at screening.
- •Positive test result for COVID-19 at Day -
- •Blood donation (excluding plasma donation) of approximately 500 mL within 56 days before screening or plasma donation within 7 days before screening.
- •Receipt of any investigational product within a time period equal to 10 half-lives of the product, if known, or a minimum of 30 days before study drug administration.
- •Consumption of alcohol within 72 hours before study drug administration.
- •Consumption of grapefruit, grapefruit products, star fruit, star fruit products, Seville oranges, or Seville orange products within the 72-hour period before study drug administration.
- •Use of tobacco or nicotine-containing products within the 6-month period preceding study drug administration.
- •Current enrollment in another clinical study.
- •Previous enrollment in any clinical study involving omaveloxolone.
研究组 & 干预措施
Sequence ABC
Subjects receive three treatments (A: omaveloxolone 450 mg, B: omaveloxolone matching placebo 450 mg and C: moxifloxacin 400 mg) administered in a single dose with the standard FDA high-fat meal in three periods. Treatment A (Period 1 from Day 1 - 15), Treatment B (Period 2 from Day 15 - 29), and Treatment C(Period 3 from Day 29 -32)
干预措施: Omaveloxolone (Drug)
Sequence ABC
Subjects receive three treatments (A: omaveloxolone 450 mg, B: omaveloxolone matching placebo 450 mg and C: moxifloxacin 400 mg) administered in a single dose with the standard FDA high-fat meal in three periods. Treatment A (Period 1 from Day 1 - 15), Treatment B (Period 2 from Day 15 - 29), and Treatment C(Period 3 from Day 29 -32)
干预措施: Moxifloxacin (Drug)
Sequence BAC
Subjects receive three treatments (A: omaveloxolone 450 mg, B: omaveloxolone matching placebo 450 mg and C: moxifloxacin 400 mg) administered in a single dose with the standard FDA high-fat meal in three periods. Treatment B (Period 1 from Day 1-15), Treatment A (Period 2 from Day 15 - 29, and Treatment C (Period 3 from Day 29 to 32)
干预措施: Omaveloxolone (Drug)
Sequence BAC
Subjects receive three treatments (A: omaveloxolone 450 mg, B: omaveloxolone matching placebo 450 mg and C: moxifloxacin 400 mg) administered in a single dose with the standard FDA high-fat meal in three periods. Treatment B (Period 1 from Day 1-15), Treatment A (Period 2 from Day 15 - 29, and Treatment C (Period 3 from Day 29 to 32)
干预措施: Moxifloxacin (Drug)
Sequence ACB
Subjects receive three treatments (A: omaveloxolone 450 mg, B: omaveloxolone matching placebo 450 mg and C: moxifloxacin 400 mg) administered in a single dose with the standard FDA high-fat meal in three periods. Treatment A (Period 1 from Day 1-15), Treatment C (Period 2 from Day 15 -18), and Treatment B (Period 3from Day 18 - 32)
干预措施: Omaveloxolone (Drug)
Sequence ACB
Subjects receive three treatments (A: omaveloxolone 450 mg, B: omaveloxolone matching placebo 450 mg and C: moxifloxacin 400 mg) administered in a single dose with the standard FDA high-fat meal in three periods. Treatment A (Period 1 from Day 1-15), Treatment C (Period 2 from Day 15 -18), and Treatment B (Period 3from Day 18 - 32)
干预措施: Moxifloxacin (Drug)
Sequence BCA
Subjects receive three treatments (A: omaveloxolone 450 mg, B: omaveloxolone matching placebo and C: moxifloxacin 400 mg) administered in a single dose with the standard FDA high-fat meal in three periods. Treatment B (Period 1 from Day 1 - 15), Treatment C (Period 2 from Day 15 to 18), and Treatment A (Period 3 from Day 18 - 32)
干预措施: Omaveloxolone (Drug)
Sequence BCA
Subjects receive three treatments (A: omaveloxolone 450 mg, B: omaveloxolone matching placebo and C: moxifloxacin 400 mg) administered in a single dose with the standard FDA high-fat meal in three periods. Treatment B (Period 1 from Day 1 - 15), Treatment C (Period 2 from Day 15 to 18), and Treatment A (Period 3 from Day 18 - 32)
干预措施: Moxifloxacin (Drug)
Sequence CAB
Subjects receive three treatments (A: omaveloxolone 450 mg, B: omaveloxolone matching placebo and C: moxifloxacin 400 mg) administered in a single dose with the standard FDA high-fat meal in three periods. Treatment C (Period 1 from Day 1 - 4), Treatment A (Period 2 from Day 4 - 18), and Treatment B (Period 3 from Day 18 - 32)
干预措施: Omaveloxolone (Drug)
Sequence CAB
Subjects receive three treatments (A: omaveloxolone 450 mg, B: omaveloxolone matching placebo and C: moxifloxacin 400 mg) administered in a single dose with the standard FDA high-fat meal in three periods. Treatment C (Period 1 from Day 1 - 4), Treatment A (Period 2 from Day 4 - 18), and Treatment B (Period 3 from Day 18 - 32)
干预措施: Moxifloxacin (Drug)
Sequence CBA
Subjects receive three treatments (A: omaveloxolone 450 mg, B: omaveloxolone matching placebo and C: moxifloxacin 400 mg) administered in a single dose with the standard FDA high-fat meal in three periods. Treatment C (Period 1 from Day 1 - 4), Treatment B (Period 2 from Day 4 - 18), and Treatment A (Period 3 from Day 18 - 32)
干预措施: Omaveloxolone (Drug)
Sequence CBA
Subjects receive three treatments (A: omaveloxolone 450 mg, B: omaveloxolone matching placebo and C: moxifloxacin 400 mg) administered in a single dose with the standard FDA high-fat meal in three periods. Treatment C (Period 1 from Day 1 - 4), Treatment B (Period 2 from Day 4 - 18), and Treatment A (Period 3 from Day 18 - 32)
干预措施: Moxifloxacin (Drug)
结局指标
主要结局
Change from baseline in placebo-corrected QTcF (∆∆QTcF)
时间窗: At Day 1 of each period, which is 14 days for both Treatment A and Treatment B and 4 days for Treatment C
The relationship between ∆QTcF and omaveloxolone and its metabolites, M17 and M22 plasma concentrations will be investigated by a linear mixed effects modeling approach with ∆ QTcF as the dependent variable, time-matched concentration of omaveloxolone and its metabolites as a continuous covariate (ie, 0 for placebo), and centered baseline QTcF as an additional covariate, treatment (active = 1; or placebo = 0) and time as categorical factors, and a random intercept and slope per subject.
次要结局
未报告次要终点