Single-center, Open, Controlled Study to Investigate the Interaction of Metamizole With the Cytochrome p450 System in Healthy Subjects by Application of the Basel Cocktail
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Cmax
研究概览
简要总结
Investigators conducted a single center, two-phased, open, controlled pharmacokinetic study to investigate the drug-drug interaction potential of metamizole. For this reason, healthy male volunteers were screened.
Enrolled participants were phenotyped on day 1 using the Basel Cocktail (phenotyping cocktail containing specific substrates for CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4). After, they received metamizole treatment for 8 days (3 grams per day). On the 8th day (day 9), they were phenotyped again with the Basel Cocktail and the respective phenotypes (d1 vs. d9) were compared.
详细描述
12 healthy male subjects meeting the inclusion and exclusion criteria were enrolled. On day 1, they ingested a capsule containing the Basel Cocktail (1A2: caffeine, 2B6: efavirenz, 2C9: flurbiprofen, 2C19: omeprazole, 2D6: metoprolol, 3A4: midazolam) in fastened state. Blood samples were withdrawn over 24 hours and the AUC ratios between metabolite and parent were calculated to determine the phenotype.
Probands began metamizole treatment (3000 mg/day) at the day of the 24h measurement. After 3-4 day, probands were returning to the facility to ensure safety during the metamizole treatment, blood cell count and metamizole metabolites were measured. After the 7 days of treatment, probands were exposed again to the Basel Cocktail in a fastened state. Probands were still exposed to metamizole to ensure potential inhibition. 24 hours plasma samples were withdrawn, area under the curve (AUC) ratios were calculated and compared to the basal state. After an end of study visit on the day of the 24h blood sample (following the second study day), probands were discharged.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
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
- •Healthy subjects aged between 18 and 45 years (inclusive) at screening
- •BMI between 18 and 28 kg/m2 (inclusive) and bodyweight at least 50 kg at screening
- •systolic blood pressure: 100-140 mmHg, diastolic blood pressure: 60-90 mmHg and heart rate: 45-90 bpm (inclusive), measured on the leading arm, in the supine position at screening
- •No clinically significant findings on the physical examination at screening
- •Signed informed consent prior to any study-mandated procedure
- •Hematology and clinical chemistry results not deviating from the normal range to clinically relevant extent at screening
- •Ability to communicate well with the investigator to understand and comply with the requirements of the study
排除标准
- •Smoking >5 cigarettes per day
- •History or clinical evidence of alcoholism or drug abuse within the 3- year period prior to screening
- •Loss of ≥250 ml of blood within 3 months prior to screening. Treatment with an investigational drug within 30 days prior to screening
- •Previous systemic treatment with any prescribed or over the counter medication (including herbal medicines such as St John's Wort) within 2 weeks prior to the intended start of the study
- •Inability to stop consumption inducing food products (e.g. grapefruit juice) 72 h before start of the study
- •Excessive caffeine consumption (>8 cups of coffee/ 8l coca cola per day)
- •Legal incapacity or limited legal capacity at screening
- •Positive results from urine drug screen at screening
- •History or clinical evidence of any disease (e.g. gastrointestinal disease: Morbus Crohn, Colitis Ulcerosa, anamnestic gastrointestinal bleeding) and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism or excretion of the study drugs, or which might increase the risk for toxicity
- •Known hypersensitivity to Metamizole (Novalgin®) or excipients of the drug formulation
- •Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
研究组 & 干预措施
Study population
All participants
干预措施: Metamizole (Drug)
结局指标
主要结局
Cmax
时间窗: 24 hours
Maximal Concentration in plasma of parent and metabolite
Effect on AUC ratio between parent and metabolite
时间窗: 12 hours
AUC ratio between parent and metabolite of specific cytochrome P450 substrates to determine a shift which may indicate either induction or inhibition of the specific cytochrome P450
tmax
时间窗: 24 hours
time to reach Cmax
次要结局
未报告次要终点