A Randomized, Positive and Placebo-Controlled Trial to Evaluate the Effects of Milademetan Administration on Cardiac Repolarization in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Number of participants with adverse events (AEs)
研究概览
简要总结
This will be a Phase 1, single-center, 2-part study in healthy subjects. Parts 1 and 2 need to be conducted in sequential order.
详细描述
Part 1 will enroll up to 3 cohorts of 6 healthy adult subjects to receive a single dose. The total duration of participation from the Screening visit to the follow-up will be up to 7 weeks (up to 45 days).
Part 2 of this study will randomize approximately 32 subjects. The total duration of participation from the Screening visit to the follow-up will be up to 8 weeks (up to 55 days).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
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
- •Is capable of understanding informed consent and is willing and able to provide written informed consent.
- •Is willing to comply with all protocol procedures.
- •Healthy, male, nonsmoking (for at least 90 days) subjects from 18 through 55 years of age, inclusive, at Screening, and healthy, female, nonsmoking (for at least 90 days) subjects of nonchildbearing potential from 18 through 55 years of age, inclusive, at Screening.
- •Body weight > 50 kg, body mass index between 18.0 and 30 kg/m2, inclusive.
排除标准
- •Past or present clinically relevant systemic disease as judged by the Investigator including, but not limited to, clinically relevant medical abnormalities such as psychiatric, neurologic, pulmonary, respiratory, cardiac, gastrointestinal, genitourinary, renal, hepatic, metabolic, endocrinologic, hematological, or autoimmune disorders making implementation of the protocol or interpretation of the study results difficult, or that would put the subject at risk by participating in the study in the opinion of the Investigator.
- •History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
- •Knowledge of any kind of cardiovascular disorder/condition/procedure known to increase the possibility of QT prolongation or a history of additional risk factors for torsade de pointes (eg, heart failure, hypokalemia, hypomagnesemia, congenital long QT syndrome, or family history of long QT syndrome, or Brugada syndrome), or cardiac conduction disorders.
- •Resting supine systolic blood pressure greater than 140 mm Hg; resting supine diastolic blood pressure greater than 90 mm Hg at Screening or Day -
- •Blood pressure measurements may be repeated once at the discretion of the Investigator.
- •Resting supine HR less than 45 beats per minute or greater than 100 beats per minute at Screening or Day -1 (may be repeated once at the discretion of the Investigator). Minor deviations are acceptable if considered to be of no clinical significance by the Investigator.
- •Abnormal 12-lead ECG at Screening or Day -1 (a single repeat is allowed), including:
- •QTcF > 450 msec
- •QRS > 110 msec
- •PR > 200 msec
- •Second or third-degree atrioventricular block
- •Any rhythm other than sinus rhythm, which is interpreted by the Investigator to be clinically significant at Screening or Day -
- •Dosing in another clinical trial within the last 30 days (or 5 half-lives, whichever is longer) prior to Day -
- •Family history of unexplainable sudden death at < 50 years of age.
- •History of unexplained loss of consciousness, unexplained syncope, unexplained irregular heartbeats or palpitations, clinically significant head injury, or near drowning with hospital admission.
- •Known allergic reactions to moxifloxacin (for Part 2 only) or any study medication or history of tendonitis or tendon rupture as a result of moxifloxacin or any other quinolone type drug use (for Part 2 only).
研究组 & 干预措施
A = Placebo (negative control)
Dosage Form: Capsules
Route of Administration: Oral
The placebo and milademetan will be identical in appearance.
干预措施: Placebo (Drug)
B = Moxifloxacin (positive control)
Dosage Form: Tablets
Route of Administration: Oral
Dosage: 400 mg
干预措施: Moxifloxacin (positive control) (Drug)
C = Milademetan
Drug: Milademetan
Dosage:
Part 1: 300, 330, 360 mg. Part 2: 260 mg single oral dose or higher, as determined in Part 1.
干预措施: Milademetan (Drug)
结局指标
主要结局
Number of participants with adverse events (AEs)
时间窗: Part 2: Up to 25 days
The intensity of all AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Incidence of laboratory abnormalities based on hematology test results
时间窗: Part 2: Up to 25 days
Hematocrit, Hemoglobin, Mean cell hemoglobin
Incidence of laboratory abnormalities based on clinical chemistry test results
时间窗: Part 2: Up to 25 days
Alanine aminotransferase, Albumin, Alkaline phosphatase, Aspartate aminotransferase
Incidence of laboratory abnormalities based on urinalysis test results
时间窗: Part 2: Up to 25 days
Bilirubin, color and appearance, glucose, ketones, protein
Vital signs measurements
时间窗: Part 2: Up to 25 days
Supine systolic blood pressure in mmHg and supine diastolic blood pressure in mmHg
Change from baseline in QT interval of the ECG
时间窗: Part 2: Up to 25 days
QT interval measured in msec
次要结局
- Observed maximum plasma concentration (Cmax)(Part 2: Up to 25 days)
- Time to observed maximum concentration (Tmax)(Part 2: Up to 25 days)
- area under the time-concentration curve from time zero to the time of the last quantifiable concentration (AUC0-tlast)(Part 2: Up to 25 days)