A Double-blind, Placebo-controlled, Randomised, First in Human Trial to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Oral Doses of C106 in Healthy Male and Female Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs)
研究概览
简要总结
This is a FIH, double-blind, placebo-controlled, within-group randomised, trial designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending oral doses of compound 106 (C106) in healthy females of non-childbearing potential and healthy males.
The trial will be conducted in 2 parts:
Part A, single ascending dose (SAD) including a food interaction cohort: safety, tolerability, and PK in healthy males and healthy females of non-childbearing potential receiving single ascending doses of C106.
Part B, multiple ascending dose (MAD): safety, tolerability, and PK in healthy males and healthy females of non-childbearing potential receiving twice daily multiple ascending doses of C106 for 8 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The IMP, i.e., the C106 and the placebo oral solutions, are identical in appearance. Both solutions are colourless to yellow. Hence, it is expected that the subjects, Investigator and other site personnel will remain unaware of treatment allocation.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Willing and able to give written informed consent for participation in the trial.
- •Healthy males and females of non-childbearing potential aged 18-65 years inclusive.
- •Body Mass Index (BMI) ≥ 18.5 and ≤ 30.0 kg/m2
- •Clinically normal medical history, physical findings, vital signs, ECG, and laboratory values at the time of screening, as judged by the Investigator
- •Women of non-childbearing potential, defined as pre-menopausal females who are sterilized (tubal ligation or permanent bilateral occlusion of fallopian tubes); or females who have undergone hysterectomy or bilateral oophorectomy; or post-menopausal defined as 12 months of amenorrhea (in questionable cases a blood sample with simultaneous detection of follicle stimulating hormone [FSH] ≥ 25 IU/L is confirmatory).
- •Male subjects must be willing to use condom or be vasectomised or practice sexual abstinence to prevent pregnancy and drug exposure of a partner and refrain from donating sperm from the date of dosing until 3 months after (last) dosing with the IMP. Their female partner of child-bearing potential must use highly effective contraceptive methods with a failure rate of < 1% to prevent pregnancy (combined [oestrogen and progestogen containing] hormonal contraception associated with inhibition of ovulation [oral, intravaginal, transdermal], progestogen-only hormonal contraception associated with inhibition of ovulation [oral, injectable, implantable], intrauterine device [IUD]or intrauterine hormone-releasing system [IUS]) from at least 4 weeks prior to dose to 3 months after last dose.
排除标准
- •History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the trial, or influence the results or the subject's ability to participate in the trial.
- •Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
- •Malignancy within the past 5 years except for in situ removal of basal cell carcinoma.
- •Any planned major surgery within the duration of the trial.
- •Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and Human Immunodeficiency Virus (HIV).
- •After 10 minutes supine rest at the time of screening, any vital signs values outside the following ranges:
- •Systolic blood pressure <90 or >140 mmHg, or
- •Diastolic blood pressure <50 or >90 mmHg, or
- •Pulse <40 or >90 bpm
- •Prolonged QTcF (>450 ms), PR interval < 120 ms or > 240 ms, QRS>115 ms, clinically significant cardiac arrhythmias or any clinically significant abnormalities in the resting ECG at the time of screening, as judged by the Investigator.
- •History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to C
- •Regular use of any prescribed or non-prescribed medication including antacids, analgesics, herbal remedies, vitamins and minerals within 2 weeks prior to the (first) administration of IMP, at the discretion of the Investigator.
- •Planned treatment or treatment with another investigational drug within 3 months prior to Day -
- •Subjects consented and screened but not dosed in previous clinical trials are not excluded.
- •Current smokers or users of nicotine products. Irregular use of nicotine (e.g., smoking, snuffing, chewing tobacco) less than three times per week is allowed before screening visit.
- •Positive screen for drugs of abuse or alcohol at screening or on admission to the unit prior to administration of the IMP.
- •History of alcohol abuse or excessive intake of alcohol, as judged by the Investigator.
- •Presence or history of drug abuse, as judged by the Investigator.
- •History of, or current use of, anabolic steroids.
- •Excessive caffeine consumption defined by a daily intake of >5 cups of caffeine containing beverages.
- •Plasma donation within one month of screening or blood donation (or corresponding blood loss) during the three months prior to screening.
- •Investigator considers the subject unlikely to comply with trial procedures, restrictions, and requirements.
研究组 & 干预措施
C106 solution
Part A: Oral administration start dose, Single dose 5 mg Part B: Oral administration start dose 20 mg twice daily for 8 days
干预措施: C106 solution (Drug)
Placebo
Part A and B: Placebo to C106 without the active pharmaceutical ingredient
干预措施: Placebo (Drug)
结局指标
主要结局
Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs)
时间窗: From date of signing informed consent until End of Study, assessed up to Day 22
AE reporting and questioning. AEs must be recorded in the AE Log of the eCRF. The Investigator must provide information on the AE, preferably with a diagnosis or at least with signs and symptoms; start and stop dates, start and stop time; intensity; causal relationship to IMP; action taken, and outcome. If the AE is serious, this must be indicated in the eCRF. AEs, including out-of-range clinically significant clinical safety laboratory values, must be recorded individually, except when considered manifestations of the same medical condition or disease state; in such cases, they must be recorded under a single diagnosis. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. The causal relationship between AEs and the IMP was assessed as related, not related or not applicable.
Number of Reported Clinically Significant Changes From Baseline in 12-lead Electrocardiograms (ECGs)
时间窗: Part A: Up to Day 10. Part B: Up to Day 22.
Single 12-lead ECG will be recorded in supine position after 10 minutes of rest using an ECG machine. Abnormalities will be specified and documented as clinically significant or not clinically significant. Heart rate (HR) and PR, QRS, QT, and QTcF intervals were recorded.
Number of Reported Clinically Significant Changes in Vital Signs
时间窗: Part A: Up to Day 3, Part B: Up to Day 10. Vital signs were measured at pre-defined timepoints during the trial.
Systolic and diastolic blood pressure and pulse were measured in supine position after 10 minutes of rest. The respiratory rate was assessed. Body temperature was measured using a digital thermometer on Day -1 of each part.
Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis)
时间窗: Part A: Up to Day 3, Part B: Up to Day 10. Safety laboratory samples were collected at pre-defined timepoints during the trial.
Blood samples for analysis of clinical chemistry, haematology, and coagulation parameters were collected through venepuncture or an indwelling venous catheter.
Number of Reported Clinically Significant Changes in Physical Examinations.
时间窗: Physical examination was performed at pre-defined timepoints during the trial. Part A: Day 7, Part B: Day 22
Any abnormalities will be specified and documented as clinically significant or not clinically significant. Abnormal findings assessed as clinically significant will be reported as AEs. A complete physical examination will include assessments of the head, eyes, ears, nose, throat, skin, neurological, lungs, cardiovascular, and abdomen. .
次要结局
未报告次要终点