Part 1: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Ascending Single Dose and Food Influence Study of QGC001 Administered Orally To Healthy Adult Subjects, Part 2: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Ascending Multiple Dose Study of QGC001 Administered Orally To Healthy Adult Subjects.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 69
- 试验地点
- 1
- 主要终点
- Haematocrit
研究概览
简要总结
1QG2 is a Phase 1 study aiming to assess the safety and tolerability of ascending single/multiple oral doses (SAD & MAD) in healthy young subjects, the preliminary food interaction and the effect of QGC001 on blood pressure and heart rate, but also to determine pharmacokinetic preliminary profiles of QGC001 and its metabolite EC33 and pharmacodynamic preliminary profiles of QGC001 and its metabolite EC33 especially effects on the renin-angiotensin-aldosterone and copeptin systems.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Caucasian, male healthy subjects of 18 to 45 years of age (inclusive).
- •Body weight ≥50 kg, with a body mass index calculated as weight in kg/(height in m2) from 18 to 27 kg/m2 at screening.
- •Subjects will sign and date an informed consent form before any study-specific screening procedure is performed.
- •Healthy, as determined by the investigator on the basis of medical history, physical examination findings, clinical laboratory test results, vital sign measurements, and digital 12 lead ECG readings.
- •Non-smoker or smoker of fewer than 5 cigarettes per day as determined by history. Must be able to abstain from smoking during the inpatient stay.
- •Have a high probability for compliance with and completion of the study.
排除标准
- •Any significant cardiovascular, hepatic, renal, respiratory, gastrointestinal, endocrine, immunologic, dermatological, haematological, neurologic, psychiatric disease or history of any clinically important drug allergy.
- •Acute disease state within 7 days before study day
- •History of drug abuse within 1 year before study day
- •History of alcoholism within 1 year before day
- •Consumption of more than 50 g of ethanol per day.
- •Positive serologic findings for human immunodeficiency virus antibodies, hepatitis B surface antigen, and/or hepatitis C virus antibodies.
- •Positive findings of urine drug screen (e.g., amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates, MDMA)
- •History of any clinically important drug allergy.
- •Prohibited Treatments: use of any investigational drug within 90 days or prescription drug within 30 days before investigational medical product administration.
- •Consumption of any caffeine-containing products in excess of 6 cups per day (or equivalent), of grapefruit, grapefruit-containing products, or alcoholic beverages within 24 hours before study day
- •Use of any over-the-counter drugs including herbal supplements (except for the occasional use of acetaminophen [paracetamol], aspirin and vitamins ≤100% recommended daily allowance) within 7 days before investigational medicinal product administration.
- •Donation of blood (i.e. 450 ml) within 90 days before study day 1.
研究组 & 干预措施
500 mg bid of QGC001
Each dose of QGC001 will be administered in solution with 200 mL of purified water.
干预措施: QGC001 [(3S,3'S)-4,4'-dithiobis (3-aminobutane-1-sulfonic acid)] (Drug)
750 mg bid of QGC001
Each dose of QGC001 will be administered in solution with 200 mL of purified water.
干预措施: QGC001 [(3S,3'S)-4,4'-dithiobis (3-aminobutane-1-sulfonic acid)] (Drug)
1,000 mg bid of QGC001
Each dose of QGC001 will be administered in solution with 200 mL of purified water.
干预措施: QGC001 [(3S,3'S)-4,4'-dithiobis (3-aminobutane-1-sulfonic acid)] (Drug)
Placebo
The placebo will be administered in solution with 200 mL of purified water.
干预措施: Placebo (Drug)
结局指标
主要结局
Haematocrit
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Adverse events
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma sodium
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma creatinine
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
White blood cell count with differential
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Platelet count
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Red blood cell count
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Haemoglobin
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma glucose
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma cholesterol
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma potassium
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma calcium
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma total bilirubin
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma conjugated bilirubin
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma Aspartate Amino Transferase (ASAT)
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma Alanine Amino Transferase (ALAT)
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma Gamma Glutamyl Transferase (GGT)
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma alkaline phosphatases
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma total protein
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma Creatine PhosphoKinase (CPK)
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma triglycerides
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Urinary pH
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Urinary protein
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Urinary glucose
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Urinary leukocytes
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Urinary nitrites
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Urinary ketones
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Urinary blood
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Weight assessment (kg)
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Body temperature (°C)
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Supine and orthostatic (systolic and diastolic) blood pressure
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Heart rate
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
12-lead ECG
时间窗: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
次要结局
- Maximum observed plasma concentration (Cmax) of QGC001(up to 3 days for SAD and FI, up to 9 days for MAD)
- Time at which Cmax is observed (tmax) of QGC001(up to 3 days for SAD and FI, up to 9 days for MAD)
- Elimination rate constant (λz) of QGC001(up to 3 days for SAD and FI, up to 9 days for MAD)
- Terminal half-life (t1/2,z) of QGC001(up to 3 days for SAD and FI, up to 9 days for MAD)
- Area Under the Concentration-time curve (AUClast and AUC0-∞) of QGC001(up to 3 days for SAD and FI, up to 9 days for MAD)
- Maximum observed plasma concentration (MRCmax) of metabolic ratios(up to 3 days for SAD and FI, up to 9 days for MAD)
- Renal clearance (CLR)(up to 2 days for SAD and FI, up to 8 days for MAD)
- Area Under the Concentration-time curve (MRAUC) of metabolic ratios(up to 3 days for SAD and FI, up to 9 days for MAD)
- Cumulative amount eliminated (Ae)(up to 2 days for SAD and FI, up to 8 days for MAD)
- Fraction recovered (Fe)(up to 2 days for SAD and FI, up to 8 days for MAD)
- Plasma renin(up to 2 days for SAD and FI, up to 8 days for MAD)
- Plasma aldosterone(up to 2 days for SAD and FI, up to 8 days for MAD)
- Plasma cortisol(up to 2 days for SAD and FI, up to 8 days for MAD)
- Plasma copeptin(up to 2 days for SAD and FI, up to 8 days for MAD)
- Urinary aldosterone(up to 2 days for SAD and FI, up to 8 days for MAD)
- Urinary cortisol(up to 2 days for SAD and FI, up to 8 days for MAD)
- Urinary sodium(up to 2 days for SAD and FI, up to 8 days for MAD)
- Urinary potassium(up to 2 days for SAD and FI, up to 8 days for MAD)
- Urinary creatinine(up to 2 days for SAD and FI, up to 8 days for MAD)
- Systolic and Diastolic Blood Pressure(up to 8 days for MAD)
- Heart Rate(up to 8 days for MAD)