A Phase I, Double-blind, Placebo-controlled, Ascending Single-dose, Safety, Tolerability and Pharmacokinetic Study of QGC001 in Healthy Male Subjects.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Plasma Alanine Amino Transferase (ALAT)
研究概览
简要总结
QGC001/1QG1 is a Phase I "first time in man" study aiming to determine the overall safety and tolerability of single ascending oral doses of QGC001 in healthy male subjects compared to placebo, as well as the pharmacokinetics of QGC001 and its metabolite EC33 and the pharmacodynamic properties of QGC001 (effects on the renin-angiotensin-aldosterone system, blood pressure and heart rate) in healthy male subjects.
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.
- •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
10 mg of QGC001
Each dose of QGC001 was administered orally with 100 mL of sterile water for irrigation at 08:00 in the morning of Day 1.
干预措施: QGC001 [(3S,3'S)-4,4'-dithiobis (3-aminobutane-1-sulfonic acid)] (Drug)
50 mg of QGC001
Each dose of QGC001 was administered orally with 100 mL of sterile water for irrigation at 08:00 in the morning of Day 1.
干预措施: QGC001 [(3S,3'S)-4,4'-dithiobis (3-aminobutane-1-sulfonic acid)] (Drug)
125 mg of QGC001
Each dose of QGC001 was administered orally with 100 mL of sterile water for irrigation at 08:00 in the morning of Day 1.
干预措施: QGC001 [(3S,3'S)-4,4'-dithiobis (3-aminobutane-1-sulfonic acid)] (Drug)
250 mg of QGC001
Each dose of QGC001 was administered orally with 100 mL of sterile water for irrigation at 08:00 in the morning of Day 1.
干预措施: QGC001 [(3S,3'S)-4,4'-dithiobis (3-aminobutane-1-sulfonic acid)] (Drug)
500 mg of QGC001
Each dose of QGC001 was administered orally with 100 mL of sterile water for irrigation at 08:00 in the morning of Day 1.
干预措施: QGC001 [(3S,3'S)-4,4'-dithiobis (3-aminobutane-1-sulfonic acid)] (Drug)
750 mg of QGC001
Each dose of QGC001 was administered orally with 100 mL of sterile water for irrigation at 08:00 in the morning of Day 1.
干预措施: QGC001 [(3S,3'S)-4,4'-dithiobis (3-aminobutane-1-sulfonic acid)] (Drug)
1,000 mg of QGC001
Each dose of QGC001 was administered orally with 100 mL of sterile water for irrigation at 08:00 in the morning of Day 1.
干预措施: QGC001 [(3S,3'S)-4,4'-dithiobis (3-aminobutane-1-sulfonic acid)] (Drug)
1,250 mg of QGC001
Each dose of QGC001 was administered orally with 100 mL of sterile water for irrigation at 08:00 in the morning of Day 1.
干预措施: QGC001 [(3S,3'S)-4,4'-dithiobis (3-aminobutane-1-sulfonic acid)] (Drug)
Placebo
The placebo was administered orally with 100 mL of sterile water for irrigation at 08:00 in the morning of Day 1.
干预措施: Placebo (Drug)
结局指标
主要结局
Plasma Alanine Amino Transferase (ALAT)
时间窗: up to 11 days
Plasma Gamma Glutamyl Transferase (GGT)
时间窗: up to 11 days
Plasma total bilirubin
时间窗: up to 11 days
Plasma conjugated bilirubin
时间窗: up to 11 days
Urinary blood
时间窗: up to 11 days
Adverse events
时间窗: up to 11 days
Blood pressure
时间窗: up to 11 days
Heart rate
时间窗: up to 11 days
Body temperature
时间窗: up to 11 days
12-lead ECG
时间窗: up to 11 days
Red blood cell count
时间窗: up to 11 days
Haemoglobin
时间窗: up to 11 days
Haematocrit
时间窗: up to 11 days
White blood cell count with differential
时间窗: up to 11 days
Plasma Aspartate Amino Transferase (ASAT)
时间窗: up to 11 days
Platelet count
时间窗: up to 11 days
Plasma sodium
时间窗: up to 11 days
Plasma potassium
时间窗: up to 11 days
Plasma calcium
时间窗: up to 11 days
Plasma alkaline phosphatases
时间窗: up to 11 days
Plasma total protein
时间窗: up to 11 days
Plasma Creatine PhosphoKinase (CPK)
时间窗: up to 11 days
Plasma creatinine
时间窗: up to 11 days
Plasma glucose
时间窗: up to 11 days
Plasma cholesterol
时间窗: up to 11 days
Urinary ketones
时间窗: up to 11 days
Plasma triglycerides
时间窗: up to 11 days
Urinary pH
时间窗: up to 11 days
Urinary protein
时间窗: up to 11 days
Urinary glucose
时间窗: up to 11 days
Urinary leukocytes
时间窗: up to 11 days
Urinary nitrites
时间窗: up to 11 days
次要结局
- Maximum observed plasma concentration (Cmax) of QGC001(H0, H 0.5, H1, H1.5, H2, H3, H4, H5, H6, H9, H12, H24 and H48 post-dose)
- Time at which Cmax is observed (tmax) of QGC001(H0, H 0.5, H1, H1.5, H2, H3, H4, H5, H6, H9, H12, H24 and H48 post-dose)
- Elimination rate constant (λz) of QGC001(H0, H 0.5, H1, H1.5, H2, H3, H4, H5, H6, H9, H12, H24 and H48 post-dose)
- Terminal half-life (t1/2,z) of QGC001(H0, H 0.5, H1, H1.5, H2, H3, H4, H5, H6, H9, H12, H24 and H48 post-dose)
- Area Under the Concentration-time curve (AUClast and AUC0-∞) of QGC001(H0, H 0.5, H1, H1.5, H2, H3, H4, H5, H6, H9, H12, H24 and H48 post-dose)
- Maximum observed plasma concentration (MRCmax) of metabolic ratios(H0, H 0.5, H1, H1.5, H2, H3, H4, H5, H6, H9, H12, H24 and H48 post-dose)
- Area Under the Concentration-time curve (MRAUC) of metabolic ratios(H0, H 0.5, H1, H1.5, H2, H3, H4, H5, H6, H9, H12, H24 and H48 post-dose)
- Cumulative amount eliminated (Ae)(H-12 to H0 pre-dose and H0- H6, H6-H12 and H12-H24 post-dose)
- Fraction recovered (Fe)(H-12 to H0 pre-dose and H0- H6, H6-H12 and H12-H24 post-dose)
- Renal clearance (CLR)(H-12 to H0 pre-dose and H0- H6, H6-H12 and H12-H24 post-dose)
- Plasma renin(H-1 pre-dose and H2, H4 and H9 post-dose)
- Plasma aldosterone(H-1 pre-dose and H2, H4 and H9 post-dose)
- Plasma cortisol(H-1 pre-dose and H2, H4 and H9 post-dose)
- Plasma copeptin(H-1 pre-dose and H2, H4 and H9 post-dose)
- Urinary aldosterone(H-12 to H0 pre-dose, H0-H6, H6-H12 and H12-H24 post-dose)
- Urinary cortisol(H-12 to H0 pre-dose, H0-H6, H6-H12 and H12-H24 post-dose)
- Urinary creatinin(H-12 to H0 pre-dose, H0-H6, H6-H12 and H12-H24 post-dose)