A Randomized, Double Blind, Placebo-controlled, Single Ascending Dose Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Single Doses of BTZ043 in Healthy Adult Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Number of participants with treatment-related adverse events concerning ECG as assessed by CTCAE v4.03 (Common Terminology Criteria for Adverse Events)
研究概览
简要总结
This study is a randomized, double-blind, placebo-controlled, single ascending dose study to evaluate safety, tolerability, and pharmacokinetics of single doses of BTZ043 in healthy adult volunteers. The study is conducted at a study centre in Germany. Up to 50 male and female participants will be included in this study in up to 5 cohorts; each cohort will consist of 10 subjects: in each cohort 8 subjects will be assigned to BTZ-043 and 2 to placebo. The doses tested will be: 125mg, 250mg, 500mg, 1000mg and 2000mg. Safety will be assessed via regular vital sign measurement, 12-lead ECG parameters, physical examination and safety laboratory assessments.
Subjects will be hospitalized from Day -1 until discharge in the morning of Day 3. After completion of all Day 3 assessments of a cohort, blinded safety data will be reviewed and the next dose increment will be decided by the Trial Steering Committee (TSC).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Subjects, investigators and investigators' staff, persons performing the assessments or being responsible for determining dosing regimen/adjustments, and staff of the sponsor or data analysts, will remain blinded from the time of randomization until database lock, using the following methods: randomization data, including any documentation identifying the treatment allocation, are kept strictly confidential until the time of unblinding with the following exceptions: staff responsible for study drug management (i.e. the staff in the CRO CTS department preparing the IMP).
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
- •Provide written informed consent
- •Healthy male or female subjects aged between ≥18 and ≤55 years at screening who are able to read, write, and fully understand the German language
- •BMI between ≥18 and ≤30 kg/m2, with a body weight between ≥55 and ≤90 kg at screening
- •Vital signs within range: pulse rate 50-90 bpm, systolic blood pressure 90-140 mmHg, diastolic blood pressure 50-90 mmHg
- •No clinically significant findings in laboratory tests
- •Women must be of non-childbearing potential, that is, either postmenopausal or premenopausal with documented tubal ligation or hysterectomy or women who are at least 6 weeks post-surgical bilateral oophorectomy
- •Male subjects must agree to use a condom with spermicide when engaging in sexual intercourse during the study period and for 2 months after study drug dosing, if they have not had a vasectomy at least 6 months before study start
- •Male subjects must not donate sperm during the study and for 2 months after study drug dosing
- •Able to swallow the amount of drug in succession
- •Agree not to donate blood (or bloodcomponents) until 1 month after receiving study drug
- •Normal consumption of alcohol
- •Willing to forgo sunbathing and prolonged exposure to sunlight during the study period
- •Willing to forgo strenuous exercise from 72 hours prior to admission until discharge
排除标准
- •Any known chronic systemic viral infection
- •Any relevant systemic infection or other systemic illness
- •Vaccination 30 days prior to drug administration
- •Known hypersensitivity to any of the excipients of the study drug
- •A clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue diseases or disorders, or have a clinically relevant surgical history or any other medical condition
- •History of or current alcohol or illicit drug abuse
- •Positive results in the urine drug screen or blood alcohol test at admission
- •Current or recent (within the past 3 months before drug administration) use of tobacco or other nicotine-containing product or positive results of cotinine test at screening or admission
- •Use of any prescription or over-the-counter (OTC) drug or herbal product within 14 days before drug administration with exception for sporadic use of ibuprofen or paracetamol for example in case of pain
- •Use of any known drug metabolism enzyme-altering drug or supplement within 14 days before dosing or consumption of foods or beverages containing grapefruit within 48 hours before admission
- •ECG findings in the screening ECG of QTcF-interval over 450 ms; atrioventricular (AV) block with PR-interval over 200 ms, prolongation of the QRS complex over 120 ms, or other changes in the ECG that are clinically relevant as per discretion of the investigator
- •Long QT syndrome, or family history of long QT syndrome or sudden death of unknown or cardiac-related cause
- •Use or planned necessary use of any QT-prolonging agents
- •Participation in another investigational drug study within the previous 30 days before drug administration
- •Any donation of blood, plasma, or platelets or significant loss of blood within the previous 30 days before drug administration
- •Previous randomization in this study
- •Volunteer unwilling or unable to comply with protocol requirements in the judgment of the investigator
- •Vulnerable subject (e.g. person is kept in detention)
- •Employees of the sponsor or subjects who are employees or relatives of the investigator
研究组 & 干预措施
Cohort 5: Placebo
N=2, matching placebo, powder and solvent for oral solution, single dose
干预措施: Placebo (Drug)
Cohort 1: 125 mg BTZ-043 fasting
N=8, 125 mg BTZ-043 fasting, oral administration, powder and solvent for oral suspension, single dose
干预措施: BTZ-043 (Drug)
Cohort 1: Placebo
N=2, matching placebo, powder and solvent for oral solution, single dose
干预措施: Placebo (Drug)
Cohort 2: 250 mg BTZ-043 fasting
N=8, 250 mg BTZ-043 fasting, oral administration, powder and solvent for oral suspension, single dose
干预措施: BTZ-043 (Drug)
Cohort 2: Placebo
N=2, matching placebo, powder and solvent for oral solution, single dose
干预措施: Placebo (Drug)
Cohort 3: 500 mg BTZ-043 fasting
N=8, 500 mg BTZ-043 fasting, oral administration, powder and solvent for oral suspension, single dose
干预措施: BTZ-043 (Drug)
Cohort 3: Placebo
N=2, matching placebo, powder and solvent for oral solution, single dose
干预措施: Placebo (Drug)
Cohort 4: 1000 mg BTZ-043 fasting
N=8, 1000 mg BTZ-043 fasting, oral administration, powder and solvent for oral suspension, single dose
干预措施: BTZ-043 (Drug)
Cohort 4: Placebo
N=2, matching placebo, powder and solvent for oral solution, single dose
干预措施: Placebo (Drug)
Cohort 5: 2000mg BTZ-043 fasting
N=8, 2000 mg BTZ-043 fasting, oral administration, powder and solvent for oral suspension, single dose
干预措施: BTZ-043 (Drug)
结局指标
主要结局
Number of participants with treatment-related adverse events concerning ECG as assessed by CTCAE v4.03 (Common Terminology Criteria for Adverse Events)
时间窗: 0.5 hours to 12.0 hours post-dosing
Measured by 12-lead ECG assessments on 6 different timepoints.
Number of participants with treatment-related adverse events concerning clinical observations as assessed by CTCAE v4.03
时间窗: 4 hours to 48 hours post-dosing
Examination of general appearance, skin, neck (including thyroid), throat, lungs, heart, abdomen, back, lymph nodes, extremities, vascular and neurological systems.
Number of participants with treatment-related adverse events concerning safety laboratory as assessed by CTCAE v4.03
时间窗: 24 hours to 26 hours post-dosing
Measured by clinical chemistry, haematology, coagulation, urinalysis on 2 different timepoints
Number of participants with treatment-related adverse events concerning vital signs as assessed by CTCAE v4.03
时间窗: 0.25 hours to 48 hours post-dosing
Measured by blood pressure, pulse rate, respiratory rate and tympanic body temperature on 7 different timepoints
次要结局
- Pharmacokinetic assessment of BTZ-043 after a single oral dose(0.25 hours to 36 hours post-dosing)
- Determining the effect of sex differences on systemic exposure by analyzing the PK of BTZ-043 in male and female participants.(0.25 hours to 36 hours post-dosing)
研究者
Michael Hoelscher
Director
Ludwig-Maximilians - University of Munich