A Dose-blocked-randomized, Double-blind, Placebo-controlled, Single and Multiple Dosing, Dose-escalation Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics/Pharmacodynamics of DDN-A-0101 in Healthy Adults and Elderly Subjects
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Assessment of safety and tolerability of DDN-A-0101 by monitoring vital signs
研究概览
简要总结
The study is a Phase I, randomized double-blind, placebo-controlled, single and multiple dosing, dose-escalation study of the oral administration of DDN-A-0101 in healthy adults and elderly subjects
详细描述
The study includes two Parts; Part1 includes single ascending dose study (SAD) and Part2 includes multiple ascending dose study (MAD). Approximately 50 subjects will be enrolled in the SAD and MAD respectively. New subjects will be recruited for each cohort in both Parts. The SAD Part will include 5 dose levels (S1, S2, S3, S4, S5) and cohort S3 will proceed to food effect cohort. The MAD Part will include 5 dose levels (M1, M2, ME, M3, M4) and cohort ME will be performed in the elderly group.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
To maintain double-blindness, DDN-A-0101 tablets and placebo with the same formulation and properties that cannot be distinguished in appearance will be used, and sub-packaging will also be the same.
入排标准
- 年龄范围
- 19 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •The subject is a healthy adult over 19 years of age and under 65 years of age*.
- •*For cohort ME (senior aged person), over 65 years old and under 75 years old a healthy volunteer
- •As a result of the body measurement at the time of screening, the subject has the body weight of 55.0 kg or more and 90.0 kg or less, and the body mass index (BMI) is 18.0 kg/m2 or more and 27.0 kg/m2 or less.
- •The subject who has listened to and listened to sufficient explanations of this clinical trial and voluntarily decided to participate in writing to faithfully implement the compliance with the clinical trial.
排除标准
- •The subject with a history of clinically significant cardiovascular system, respiratory system, kidney, endocrine system, blood system, digestive system, central nervous system, urinary system, musculoskeletal system, psychiatric disease (mood disorders, obsessive-compulsive disorders, etc.) or malignancies (but can be registered if the past history of complete recovery does not affect the current health condition).
- •The subject with a history of gastrointestinal diseases (such as Crohn's disease, ulcers, acute or chronic pancreatitis, hypothyroidism, anaphylaxis, etc.) or gastrointestinal operations (except simple appendectomy or hernia) that may affect the absorption of clinical trials drugs.
- •The subject diagnosed with peptic ulcer, esophageal disease, and Zollinger-Ellison syndrome within 90 days prior to clinical trial drug administration and have been treated or have a medical history or symptoms clinically suspicious of it.
- •The subject showing the following values in the laboratory test results.
- •Blood aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level > 1.5 times normal upper limit
- •Blood Total bilirubin level > 1.5 times normal upper limit
- •Blood creatine phosphokinase (CPK) level > 1.5 times normal upper limit
- •Positive serum epidemiological test results (human immunodeficiency virus (HIV) Ag/Ab, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) Ab, Syphilis regain test)
- •Chronic kidney disease epidemiology collaboration (CKD-EPI) equation calculated creatine cleaning rate: < 60 mL/min/1.73 m2
- •The subject with significant abnormalities in neurological examinations conducted during screening visits.
- •The subject who showed systolic blood pressure ≥ 150 mmHg or < 90 mmHg, diastolic blood pressure ≥ 100 mmHg or < 50 mmHg in blood pressure measured from the upper left after resting for at least 5 minutes at the time of screening.
- •The subject with clinically significant allergic diseases (excluding mild allergic rhinitis that does not require administration)
- •The subject who have a history of drug abuse or are positive for an abuse drug in a urine screening test.
- •The subject who have a history of hypersensitivity reactions to drugs of the same class as the main ingredient and component components of clinical trial drugs.
- •The subject who have received medications from other clinical trials and biological equivalence trials within 6 months of the start of administration of clinical trials.
- •The subject who took metabolic enzyme-induced and inhibitory drugs such as barbital drugs within 30 days prior to administration of clinical trial drugs.
- •The subject who have donated whole blood within 60 days prior to administration of clinical trial drugs or volunteers who have donated or received component blood within 20 days prior to administration of clinical trial drugs.
- •The subject who took over-the-counter drugs or herbal medicines within 14 days of clinical trial administration, or took over-the-counter drugs, health functional foods, or vitamins within 7 days (but may participate in clinical trials if it is deemed that the results of the clinical trial are not affected by the examiner's judgment).
- •The subject who cannot prohibit the administration of the following drugs during the clinical trial period from 8 weeks before the scheduled date of the first administration of the drug for clinical trial.
- •Dementia medications, cognitive enhancers, choline agonists, anti-choline agonists, anti-Parkinson drugs
- •Medicines/supplements/health functional foods and other cosmetics (shampoo, lotion, etc.) containing Houttuynia cordata extract, the main ingredient of this clinical trial drug
- •Medicines or health functional foods with similar indications to other clinical medicines (e.g., extracts derived from ginkgo leaves, etc.)
- •The subject who consumed grapefruit-containing food (one grapefruit or more than 200 ml of grapefruit juice) within 7 days prior to administration of clinical trial drugs.
- •The subject who are forced to consume caffeine (coffee, green tea, etc. >5 cups/day) continuously or consume caffeine-containing food 24 hours before hospitalization during the clinical trial period.
- •The subject who are unable to drink alcohol continuously (alcohol > 210 g/shareholder) or abstain from drinking during clinical trials 24 hours before hospitalization.
- •The subject who cannot smoke excessively (tobacco > 10 skins/day) or quit smoking during the clinical trial period from 24 hours before hospitalization
- •The subject who is pregnant or breast-feeding.
- •The subject who do not agree to use one or more medically acceptable forms of contraception during the pre-clinical period and until at least 90 days after the last clinical trial administration, and those who do not agree to donate sperm or eggs until at least 90 days after the last clinical trial administration. Medically acceptable forms of contraception are as follows.
- •Use of an intrauterine device with proven pregnancy failure rates in the person or partner
- •Use both blocking contraceptives (for male or female use) and spermicide
- •Surgery by yourself or your partner (vasectomy, salpingectomy/ligation, hysterectomy)
- •The subject with a history of suicidal behavior and/or ongoing suicidal ideation following C-SSRS evaluation when screening.
- •The subject deemed unsuitable for participation in clinical trials due to other reasons other than the criteria for exclusion above.
研究组 & 干预措施
Experimental: DDN-A-0101 for PART 1
DDN-A-0101: various single doses, administered to various cohorts
干预措施: DDN-A-0101 (SAD) (Drug)
Experimental: DDN-A-0101 for PART 2
DDN-A-0101: various multiple doses, administered to various cohorts
干预措施: DDN-A-0101 (MAD) (Drug)
Placebo Comparator: Placebo for PART 1
DDN-A-0101 matching placebo: various single doses, administered to various cohorts
干预措施: Placebo (SAD) (Drug)
Placebo Comparator: Placebo for PART 2
DDN-A-0101 matching placebo: various multiple doses, administered to various cohorts
干预措施: Placebo (MAD) (Drug)
结局指标
主要结局
Assessment of safety and tolerability of DDN-A-0101 by monitoring vital signs
时间窗: through study completion (up to Day 12 for SAD test, Day 25 for MAD test)
Body temperature (°C) measurement to assess vital signs after DDN-A-0101 administration
Assessment of safety and tolerability of DDN-A-0101 by monitoring ECG
时间窗: through study completion (up to Day 12 for SAD test, Day 25 for MAD test)
12-ECG electrocardiogram test includes measurement of P-wave (reflecting atrial depolarization), QRS complex (reflecting depolarization of ventricles) and QT interval (reflecting the total duration of ventricular depolarization and repolarization
Assessment of safety and tolerability of DDN-A-0101 by C-SSRS measurement
时间窗: through study completion (up to Day 12 for SAD test, Day 25 for MAD test)
Columbia-suicide severity rating scale (C-SSRS) includes the measurement of the incidences and severity of suicidal thoughts
Assessment of pharmacokinetics of Quercitrin in urine
时间窗: up to 48 hour after intervention
Renal clearance (CL) of Quercitrin
Assessment of pharmacokinetics of Quercitrin, an indicator of of DDN-A-0101 in plasma
时间窗: up to 48 hour after intervention
Area under curve (AUC) in plasma
Assessment of safety and tolerability of DDN-A-0101 by laboratory safety tests
时间窗: through study completion (up to Day 12 for SAD test, Day 25 for MAD test)
Laboratory safety tests include urine test for measurement of albumin/creatinine ratio (mg/g)
Assessment of pharmacokinetics of Quercitrin in plasma
时间窗: up to 48 hour after intervention
Accumulation index (AI) in plasma
次要结局
- Assessment of pharmacodynamics of DDN-A-0101 for PART2 MAD test(up to 24 hour after intervention)